Microvesicles derived from mesenchymal stem cells inhibit acute respiratory distress syndrome-related pulmonary fibrosis in mouse partly through hepatocyte growth factor

BACKGROUND Pulmonary fibrosis is one of the main reasons for the high mortality rate among acute respiratory distress syndrome(ARDS)patients.Mesenchymal stromal cell-derived microvesicles(MSC-MVs)have been shown to exert antifibrotic effects in lung diseases.AIM To investigate the effects and mechanisms of MSC-MVs on pulmonary fibrosis in ARDS mouse models.METHODS MSC-MVs with low hepatocyte growth factor(HGF)expression(siHGF-MSC-MVs)were obtained via lentivirus transfection and used to establish the ARDS pulmonary fibrosis mouse model.Following intubation,respiratory mechanics-related indicators were measured via an experimental small animal lung function tester.Homing of MSC-MVs in lung tissues was investigated by near-infrared live imaging.Immunohistochemical,western blotting,ELISA and other methods were used to detect expression of pulmonary fibrosis-related proteins and to compare effects on pulmonary fibrosis and fibrosis-related indicators.RESULTS The MSC-MVs gradually migrated and homed to damaged lung tissues in the ARDS model mice.Treatment with MSC-MVs significantly reduced lung injury and pulmonary fibrosis scores.However,low expression of HGF(siHGF-MSC-MVs)significantly inhibited the effects of MSC-MVs(P<0.05).Compared with the ARDS pulmonary fibrosis group,the MSC-MVs group exhibited suppressed expression of type I collagen antigen,type III collagen antigen,and the proteins transforming growth factor-βandα-smooth muscle actin,whereas the siHGF-MVs group exhibited significantly increased expression of these proteins.In addition,pulmonary compliance and the pressure of oxygen/oxygen inhalation ratio were significantly lower in the MSC-MVs group,and the effects of the MSC-MVs were significantly inhibited by low HGF expression(all P<0.05).CONCLUSION MSC-MVs improved lung ventilation functions and inhibited pulmonary fibrosis in ARDS mice partly via HGF mRNA transfer.

Prognostic significance of nuclear hepatoma-derived growth factor expression in gallbladder cancer

AIM: To assess the expression of nuclear hepatoma-derived growth factor (HDGF) in benign and malignant gallbladder lesions and to determine its clinicopathological significance.

Decreased serum platelet derived growth factor BB levels in acute and increased in chronic pancreatitis

AIM: To examine circulating growth factor concentrations in patients with acute pancreatitis (AP) and chronic pancreatitis (CP), and walled-off pancreatic necrosis (WOPN).

Prolonged propagation of rat neural stem cells relies on inhibiting autocrine/paracrine bone morphogenetic protein and platelet derived growth factor signals

Continuous expansion of rat neural stem cell lines has not been achieved due to proliferation arrest and spontaneous differentiation in vitro. In the current study, neural precursor cells derived from the subventricular zone of adult rats spontaneously underwent astroglial and oligodendroglial differentiation after limited propagation. This differentiation was largely induced by autocrine or paracrine bone morphogenetic protein and platelet derived growth factor signals. The results showed that, by inhibiting bone morphogenetic protein and platelet derived growth factor signals, adult rat neural precursor cells could be extensively cultured in vitro as tripotent stem cell lines. In addition to adult rat neural stem cells, we found that bone morphogenetic protein antagonists can promote the proliferation of human neural stem cells. Therefore, the present findings illustrated the role of autocrine or paracrine bone morphogenetic protein and platelet derived growth factor signaling in determining neural stem cell self-renewal and differentiation. By antagonizing both signals, the long-term propagation of rat neural stem cell lines can be achieved.

Three important components in the regeneration of the cavernous nerve： brain-derived neurotrophic factor, vascular endothelial growth factor and the JAK/STAT signaling pathway

Retroperitoneal operations, such as radical prostatectomy, often damage the cavernous nerve, resulting in a high incidence of erectile dysfunction. Although improved nerve-sparing techniques have reduced the incidence of nerve injury, and the administration of phosphodiesterase type 5 inhibitors has revolutionized the treatment of erectile dysfunction, this problem remains a considerable challenge. In recent years, scientists have focused on brain-derived neurotrophic factor and vascular endothelial growth factor in the treatment of cavernous nerve injury in rat models. Results showed that both compounds were capable of enhancing the regeneration of the cavernous nerve and that activation of the Janus kinase （JAK）/signal transducer and activator of transcription （STAT） pathway played a major role in the process.

Pirfenidone suppresses the abnormal activation of human Müller cells after platelet-derived growth factor-BB stimulation

AIM: To determine the effect of pirfenidone on the activated human Müller cells by platelet-derived growth factor-BB(PDGF-BB). METHODS: The primary human Müller cells were separated from retinal tissues and established the pathogenic model by stimulated with PDGF-BB. The Müller cells behaviour of normal group and the model group was measured by MTT assay, Trypan blue assay, cell migration assay, and collagen contraction assay. The expression of transforming growth factor(TGF)-β1,-β2, and pigment epithelium-derived factor(PEDF) was estimated with realtime polymerase chain reaction(PCR), Western blot and immunofluorescence analyses. RESULTS: A pathogenic/proliferative model of Müller cells was established by stimulating normal cultured Müller cells with 10 ng/mL PDGF-BB for 48 h. After treated with 0.2 and 0.3 mg/mL pirfenidone, the proliferation, migration and collagen contraction was statistically significantly depressed in the model group compared with the normal groups. The expression levels of TGF-β1 and TGF-β2 were significantly down-regulated, while the PEDF expression was significantly up-regulated after treated with 0.2 and 0.3 mg/mL pirfenidone in the model group. CONCLUSION: Pirfenidone effectively suppress the proliferation, migration and collagen contraction of the human Müller cells stimulated with PDGF-BB through down-regulation of TGF-β1/TGF-β2 and up-regulation of PEDF.

Implication of platelet-derived growth factor receptor alpha in prostate cancer skeletal metastasis

Metastasis represents by far the most feared complication of prostate carcinoma and is the main cause of death for patients.The skeleton is frequently targeted by disseminated cancer cells and represents the sole site of spread in more than 80% of prostate cancer cases.Compatibility between select malignant phenotypes and the microenvironment of colonized tissues is broadly recognized as the culprit for the organ-tropism of cancer cells.Here,we review our recent studies showing that the expression of platelet-derived growth factor receptor alpha(PDGFR a) supports the survival and growth of prostate cancer cells in the skeleton and that the soluble fraction of bone marrow activates PDGFR a in a ligand-independent fashion.Finally,we offer pre-clinical evidence that this receptor is a viable target for therapy.

Deficiency of platelet-derived growth factor receptor-α-positive cells in Hirschsprung's disease colon

AIM: To investigate whether the expression of platelet-derived growth factor receptor-α-positive (PDGFRα+)-cells is altered in Hirschsprung’s disease (HD).METHODS: HD tissue specimens (n = 10) were collected at the time of pull-through surgery, while colonic control samples were obtained at the time of colostomy closure in patients with imperforate anus (n = 10). Immunolabelling of PDGFRα+-cells was visualized using confocal microscopy to assess the distribution of these cells, while Western blot analysis was undertaken to quantify PDGFRα protein expression.RESULTS: Confocal microscopy revealed PDGFRα+-cells within the mucosa, myenteric plexus and smooth muscle in normal controls, with a marked reduction in PDGFRα+-cells in the HD specimens. Western blotting revealed high levels of PDGFRα protein expression in normal controls, while there was a striking decrease in PDGFRα protein expression in the HD colon.CONCLUSION: These findings suggest that the altered distribution of PDGFRα+-cells in both the aganglionic and ganglionic HD bowel may contribute to the motility dysfunction in HD.

Expression and functional characterization of platelet-derived growth factor receptor-like gene

AIM:To investigate the role of platelet-derived growth factor receptor-like gene(PDGFRL)in the anti-cancer therapy for colorectal cancers(CRC).METHODS:PDGFRL mRNA and protein levels were measured by reverse transcription-polymerase chain reaction(RT-PCR)and immunohistochemistry in CRC and colorectal normal tissues.PDGFRL prokaryotic expression vector was carried out in Escherichia coli(E.coli),and purified by immobilized metal affinity chromatography.The effect of PDGFRL protein on CRC HCT-116 cells was detected by 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide(MTT),clone counting,cell cycle,and wound healing assay.RESULTS:Both RT-PCR and immunohistochemistry showed that the expression of PDGFRL in colorectal normal tissues was higher than in cancer tissues.Recombinant pET22b-PDGFRL prokaryotic expression vector was successfully expressed in E.coli,and the target protein was expressed in the form of inclusion bodies.After purification and refolding,recombinant human PDGFRL(rhPDGFRL)could efficiently inhibit the proliferation and invasion of CRC HCT-116 cells detected by MTT,clone counting and wound healing assay.Moreover,rhPDGFRL arrested HCT-116 cell cycling at the G0/G1 phase.CONCLUSION:PDGFRL is a potential gene for application in the anti-cancer therapy for CRC.

Effect of recombinant human platelet-derived growth factor B on cat corneal endothelial cell viability mediated by adeno-associated virus

AIM: To transduce recombinant human platelet-derived growth factor B (PDGF-B) gene adeno-associated virus(AAV) to in vitro cultured cat corneal endothelial cell (CEC) and observe the effect of the expressed PDGF-BB protein on the viability of cat CEC. METHODS: Cat cornea endothelium was torn under microscope and rapidly cultivated in DMEM to form single layer CEC and the passage 2 endothelial cells were used in this study. The recombinant human PDGF-B gene AAV was constructed and transduced into cat CEC directly. Three groups were as following: blank control group, AAV control group and recombinant AAV group. At 24 hours, 48 hours, and 5 days after transduction, total RNA was extracted from the CEC by Trizol and the expression of PDGF-B gene was detected by fluorescence quantitative polymerase chain reaction. Viability of the transduced CEC was detected at 48 hours after transduction by MTT assay. Cell morphology was observed under inverted phase contrast microscope. RESULTS: With the torn endothelium culture technique, we rapidly got single layer cat CEC. At 24 hours, 48 hours and 5 days after transduction, fluorescence quantitative polymerase chain reaction showed there was no significant difference of the expressed PDGF-B gene mRNA between blank control group and AAV control group (P>0.05). In contrast, there were significant differences between two control groups and recombinant AAV group (P<0.05). MTT assay showed that in recombinant AAV group, the expressed PDGF-BB protein could promote the viability of cat CEC. Morphology observation showed at 48 hours after transduction, cells in CEC-AAV-PDGF-B group proliferated into bigger scales in regular triangle to hexagon shape with distinct boundary, while the number of cells was significantly less in the two control groups. CONCLUSION: The recombinant AAV-PDGF-B expresses biological active PDGF-BB protein in cat CEC, which promotes the viability and proliferation of cells.

Vascular endothelial growth factor/platelet-derived growth factor receptor pathway is involved in bone marrow mesenchymal stem cell differentiation and directional migration toward gliomas

BACKGROUND： Vascular endothelial growth factor （VEGF） induces bone marrow-derived mesenchymal stem cell （BMSC） differentiation into vascular endothelial-like cells and promotes BMSC migration toward gliomas. However, the molecular mechanisms by which VEGF induces BMSC differentiation and migration remain poorly understood. OBJECTIVE; To investigate the role of platelet-derived growth factor （PDGF） receptor （PDGFR） in BMSC differentiation and migration induced by VEGE DESIGN, TIME AND SETTING： A parallel, controlled, in vitro experiment was performed at the Molecular Neurobiology ＆ Neural Regeneration and Repairing Laboratory, Anhui Provincial Hospital of Anhui Medical University, China from June 2008 to March 2009. MATERIALS： U87 glioma cells were purchased from Shanghai Institutes for Biological Sciences; mouse anti-human PDGFR and VEGF receptor （VEGFR） monoclonal antibodies were purchased from Peprotech, USA. METHODS： Isolated BMSCs were precultured with neutralizing antibody for VEGFR-1, VEGFR-2, PDGFR-α, and PDGFR-β to block biological activity of related receptors, followed by induced differentiation with 50μg/L VEGF. BMSCs induced with 50μg/L VEGF alone served as the VEGF-induced group. The control group remained untreated. MAIN OUTCOME MEASURES： Cell surface markers were identified by flow cytometry; BMSC surface cytokine receptor expression was detected by reverse transcription-polymerase chain reaction; the Transwell model was used to observe cell migration. RESULTS： After blocking the PDGFR, VEGF did not induce BMSC cell surface marker CD-31 or von Willebrand factor （vWF） expression. However, inhibition with VEGF receptor blocking agents, VEGF induced BMSCs to express CD-31 and vWE Following inhibition of the PDGFR, the number of cells migrating through the polycarbonate membrane Transwell chamber was decreased, as well as the number of BMSCs migrating to glioma cells. However, through the use of VEGF receptor blocking agents, the number of migrating cells remained unchanged. VEGF preculture increased the number of BMSCs migrating to gliomas. CONCLUSION： VEGF interacts with PDGFRs on the BMSC surface to attract BMSC directional migration and induce BMSC differentiation. The VEGF/PDGFR pathway participates in BMSC directional migration to glioma. VEGF pretreatment increased efficiency of BMSC migration to glioma.

Platelet-derived growth factor signaling in human malignancies

Platelet-derived growth factors (PDGFs) and their receptors were identified and purified decades ago. PDGFs are important during normal development and in human cancers. In particular, autocrine PDGF signaling has been implicated in various types of malignancies such as gliomas and leukemia. In contrast, paracrine signaling was found in cancers that originate from epithelial cells, where it may be involved in stromal cell recruitment, metastasis, and epithelial-mesenchymal transition. This editorial briefly discusses autocrine and paracrine PDGF signaling and their roles in human cancers, and introduces a series of review articles in this issue that address the possible roles of PDGFs in various processes involved in different types of cancers.

Clinical Significance of Platelet-Derived Growth Factor-C Expression in Colorectal Cancer

Platelet-derived growth factors (PDGFs) are known to be associated with tumor growth and angiogenesis through their activation of the receptor tyrosine kinases, PDGF receptors alpha and beta. Several studies revealed the participation of the PDGF family in colorectal cancer (CRC). However, the role of platelet derived growth factor-C (PDGFC) in CRC is less well studied. This study aimed to determine the correlation between PDGFC expression and the prognosis of patients with CRCs. Tumor samples were obtained from patients with CRC who underwent surgical resection between 2002 and 2006. The mRNA expression of PDGFC was investigated by quantitative reverse transcription-polymerase chain reaction in 85 patients with stage I-IV CRC. PDGFC protein expression was analyzed by immunohistochemistry, and the relationship between PDGFC protein expression and clinicopathologic features was investigated in 245 patients with stage I-III CRC. PDGFC mRNA expression in cancer tissues was significantly higher in patients with distant metastases than in those without metastases (P = 0.016). PDGFC protein overexpression was associated with significantly worse overall and relapse-free survival (P P < 0.0001, respectively). Moreover, PDGFC protein overexpression was an independent risk factor for CRC recurrence (relative risk = 3.395, 95% confidence interval = 1.895 - 6.081, P < 0.001). In the present study, PDGFC overexpression appeared to be predictive of recurrence and poor prognosis in patients with CRC.

Secretion of nerve growth factor,brain-derived neurotrophic factor,and glial cell-line derived neurotrophic factor in co-culture of four cell types in cerebrospinal fluid-containing medium

The present study co-cultured human embryonic olfactory ensheathJng cells, human Schwann cells, human amniotic epithelial cells and human vascular endothelial cells in complete culture medium- containing cerebrospinal fluid. Enzyme linked immunosorbent assay was used to detect nerve growth factor, brain-derived neurotrophic factor, and glial cell line-derived neurotrophic factor secretion in the supernatant of co-cultured cells. Results showed that the number of all cell types reached a peak at 7-10 days, and the expression of nerve growth factor, brain-derived neurotrophic factor, and glial cell line-derived neurotrophic factor peaked at 9 days. Levels of secreted nerve growth factor were four-fold higher than brain-derived neurotrophic factor, which was three-fold higher than glial cell line-derived neurotrophic factor. Increasing concentrations of cerebrospinal fluid （10%, 20% and 30%） in the growth medium caused a decrease of neurotrophic factor secretion Results indicated co-culture of human embryonic olfactory ensheathing cells, human Schwann cells human amniotic epithelial cells and human vascular endothelial cells improved the expression of nerve growth factor, brain-derived neurotrophic factor, and glial cell line-derived neurotrophic factor. The reduction of cerebrospinal fluid extravasation at the transplant site after spinal cord injury is beneficial for the survival and secretion of neurotrophic factors from transplanted cells.

Neuron-like differentiation of adult rat bone marrow stromal cells induced by transforming growth factor-beta and brain-derived neurotrophic factor

BACKGROUND： It has been demonstrated that transforming growth factor-β （TGF-β） and brain- derived neurotrophic factor （BDNF） can induce stem cell differentiation into neuron-like cells. OBJECTIVE： To investigate the efficacy of TGF-β and BDNF at inducing the differentiation of adult rat bone marrow stromal cells （BMSCs） into neuron-like cells, both in combination or alone. DESIGN, TIME AND SETTING： A comparative observation experiment was performed at the Department of Orthopedics, First Affiliated Hospital of Liaoning Medical University between October 2007 and January 2008. MATERIALS： TGF-~ and BDNF were purchased from Sigma, USA; mouse anti-rat neuron specific enolase, neurofilament and glial fibrillary acidic protein were purchased from Beijing HMHL Biochem Ltd., China. METHODS： BMSCs were isolated from rats aged 4 weeks and incubated with TGF-β（1μ g/L） and/or BDNF （50 μ g/mL）. MAIN OUTCOME MEASURES： Expression of neuron-specific enolase, neurofilament and glial fibrillary acidic protein were determined by immunocytochemistry. RESULTS： BMSCs differentiated into neuron-like cells following induction of TGF-β and BDNF, and expressed both neuron-specific enolase and neurofilament. The percent of positive cells was significantly greater in the combination group than those induced with TGF-β or BDNF alone （P 〈 0.01）. CONCLUSION： Treatment of BMSCs with a combination of TGF-β and BDNF induced differentiation into neuron-like cells, with the induction being significantly greater than with TGF-β or BDNF alone.

Association of hepatocyte-derived growth factor receptor/caudal type homeobox 2 co-expression with mucosal regeneration in active ulcerative colitis

AIM:To characterize the regeneration-associated stem cell-related phenotype of hepatocyte-derived growth factor receptor(HGFR)-expressing cells in active ulcerative colitis(UC).METHODS:On the whole 38 peripheral blood samples and 38 colonic biopsy samples from 18 patients with histologically proven active UC and 20 healthy control subjects were collected.After preparing tissue microarrays and blood smears HGFR,caudal type homeobox 2(CDX2),prominin-1(CD133) and Musashi-1conventional and double fluorescent immunolabelings were performed.Immunostained samples were digitalized using high-resolution Mirax Desk instrument,and analyzed with the Mirax TMA Module software.For semiquantitative counting of immunopositive lamina propria(LP) cells 5 fields of view were counted at magnification x 200 in each sample core,then mean ± SD were determined.In case of peripheral blood smears,30 fields of view with 100 μm diameter were evaluated in every sample and the number of immunopositive cells(mean ± SD) was determined.Using 337 nm UVA Laser MicroDissection system at least 5000 subepithelial cells from the lamina propria were collected.Gene expression analysis of HGFR,CDX2,CD133,leucine-rich repeat-containing G-protein coupled receptor 5(Lgr5),Musashi-1 and cytokeratin20(CK20) were performed in both laser-microdisscted samples and blood samples by using real time reverse transcription polymerase chain reaction(RT-PCR).RESULTS:By performing conventional and double fluorescent immunolabelings confirmed by RT-PCR,higher number of HGFR(blood:6.7 ± 1.22 vs 38.5 ±3.18;LP:2.25 ± 0.85 vs 9.22 ± 0.65;P < 0.05),CDX2(blood:0 vs 0.94 ± 0.64;LP:0.75 ± 0.55 vs 2.11± 0.75;P < 0.05),CD133(blood:1.1 ± 0.72 vs 8.3± 1.08;LP:11.1 ± 0.85 vs 26.28 ± 1.71;P < 0.05)and Musashi-1(blood and LP:0 vs scattered) positive cells were detected in blood and lamina propria of UC samples as compared to controls.HGFR/CDX2(blood:0 vs 1± 0.59;LP:0.8 ± 0.69 vs 2.06 ± 0.72,P < 0.05)and Musashi-1/CDX2(blood and LP:0 vs scattered) coexpressions were found in blood and lamina propria of UC samples.HGFR/CD133 and CD133/CDX2 coexpressions appeared only in UC lamina propria samples.CDX2,Lgr5 and Musashi-1 expressions in UC blood samples were not accompanied by CK20 mRNA expression.CONCLUSION:In active UC,a portion of circulating HGFR-expressing cells are committed to the epithelial lineage,and may participate in mucosal regeneration by undergoing mesenchymal-to-epithelial transition.

KIT and platelet-derived growth factor receptor α wild-type gastrointestinal stromal tumor associated with neurofibromatosis type 1: Two case reports

BACKGROUND Gastrointestinal stromal tumors(GISTs) associated with neurofibromatosis are uncommon compared to their gastrointestinal counterparts. Patients with neurofibromatosis type 1(NF-1) have an increased risk of developing gastrointestinal tumors, including rare types such as GIST.CASE SUMMARY A 60-year-old male Chinese patient was diagnosed with NF-1 10 years ago and presented with upper abdominal discomfort and black stools. Endoscopic ultrasonography and an enhanced abdominal computed tomography scan revealed a mass located 4 cm from the muscular layer of the descending duodenum. A 59-year-old Chinese woman who was diagnosed with NF-1 25 years ago presented with sudden unconsciousness and black stools. Multiple masses in the duodenum were noted by echogastroscopy and an enhanced abdominal computed tomography scan. Both patients presented with cutaneous neurofibromas. The histologic examination of tumors from both patients revealed spindle cells and low mitotic activity. Immunohistochemically, the tumor cells showed strong positivity for KIT(CD117), DOG-1, CD34, and Dehydrogenase Complex Subunit B, and negativity for SMA, desmin, S-100, and β-catenin. None of the six tumors from two patients had KIT exon 9, 11, 13, or 17 or platelet-derived growth factor receptor α exon 12 or 18 mutation, which is a typical finding for sporadic GISTs. None of the six tumors from the two patients had a BRAFV600 E mutation. The patients were alive and well during the follow-up period(range:0.6-5 yr).CONCLUSION There have been only a few previous reports of GISTs associated with NF-1.Although GISTs associated with NF-1 have morphologic and immunohistochemical similarities with GISTs, the pathogenesis, incidence,genetic background, and prognosis are not completely known. A medical history of NF-1 in a patient who has gastrointestinal bleeding or anemia and an intraabdominal mass with nonspecific computed tomography features may help in diagnosing GIST by virtue of the well-known association of these two entities.Molecular genetic studies of cases indicated that GISTs in NF-1 patients have a different pathogenesis than sporadic GISTs.

Distribution of platelet-derived growth factor-alpha receptor expressing oligodendrocyte precursor cells in the adult rat brain

BACKGROUND： Studies have demonstrated that NG2-positive glial cells in the adult rats are predominantly located in the gray and white matter of the cerebral cortex and hippocampus. Platelet-derived growth factor-a receptor （PDGF-αR） cells are a subset of oligodendrocytes, which are not as mature as NG2-positive cells. Distribution and migration of PDGF-αR-positive cells in the rat brain remain poorly understood. OBJECTIVE： Using immunohistochemical methods, the distribution of oligodendrocyte precursor cells （PDGF-αR-positive） was analyzed in the adult rat brain. DESIGN, TIME AND SETTING： Immunohistochemical study was performed at the Department of Histology and Embryology of the Third Military Medical University from September 2007 to September 2008. MATERIALS： Rabbit anti-PDGF-αR polyclonal antibody was purchased from Santa Cruz Biotechnology, USA. Streptomycin-avidin-biotin complex immunohistochemistry kit was purchased from Zhongshan Goldenbridge Biotechnology, China. METHODS： Whole brains from 5 healthy, adult, Wistar rats were collected for immunohistochemistry, and the mean value of PDGF-αR-expressing cells was quantified. The absolute values were translated to ranked data of high, moderate, and low grades （high grade： 10 positive cells; moderate grade： 5-9 cells; low grade： 〈 5 cells in a 400 × visual field）. Based on the number of cell processes and branches, as well as the number of PDGF-αR-positive cells, in different regions, the cells were classified into three categories, i.e., type Ⅰ-Ⅲ. From type I to type Ill, the number of processes gradually increased. MAIN OUTCOME MEARSURES： The number and distribution of PDGF-αR-positive cells in different brain regions of adult rats. RESULTS： PDGF-αR-positive cells were located in the forebrain and midbrain, but not in the cerebellum or brainstem. In the olfactory bulb and hippocampus, a total of 60% PDGF-αR-positive cells were type Ⅰ and these cells were not mature as others. In the cerebral cortex, olfactory system, hippocampus, and optic chiasma, where neuronal bodies aggregated, approximately 40% of the PDGF-αR-positive cells were type Ⅱ, with few type Ⅲ cells. In the white matter, corpus callosum, basal nucleus, and thalamus, PDGF-αR-positive cell density was moderate. In the olfactory bulb and hippocampus, PDGF-αR-positive cell density was high. PDGF-αR-positive cells were not observed in the cerebellum or brainstem CONCLUSION： PDGF-αR-positive cells were aggregated in the olfactory bulb and hippocampus in the adult, rat brain, but few cells were detected in the cerebellum and brainstem.

Effect of Retinoic acid on Platelet-derived Growth Factorand Lung Development in Newborn Rats

Summary: The influence of platelet-derived growth factor (PDGF) on lung development in newborn rats and the effect of retinoic acid (RA) on PDGF in lung development were investigated. Newborn Sprague-Dawley (SD) rats were randomly assigned to two groups: control group and RA group. The rats in RA group was intraperitoneally injected with all trans-retinoic acid (500 μg/kg every day) for consecutive 3 days after birth, while those in the control group were not subjected to intervention. Immunohistochemical assay was performed to locate the expression of PDGF. mRNA levels of PDGF were measured by reverse transcription polymerase chain reaction (RT-PCR) at age of 1, 3, 5, 7, 10, 14, 21 days. The method of radial alveolar counts (RAC) was used to measure the amount of the alveoli of the lungs. It was found that with increasing days, levels of PDGF-A and PDGF-B changed to verying degrees. RA could elevate significantly the expression levels of PDGF-A mRNA and protein (P<0.01), but not affect the expression levels of PDGF-B mRNA and protein markedly (P>0.05). It is suggested that PDGF might play an important role in lung development. RA can stimulate lung development through increasing the expression levels of PDGF-A mRNA and protein.

Effects of interleukin-1α on platelet-derived growth factor release from bovine cerebral microvascular endothelial cells

The present study showed that, interleukin-1α (IL-1α) stimulateal cultured bovine cerebral microvascular endothelial cells (BCMEC) releasing growth factor which promoted bovine cerebral microvascular smooth muscle cells (BCMSMC) proliferation in a dose-dependent manner. The mitogenic activity in conditioned medium of BCMEC stimulated by IL-1α was neutralized significantly by the antibody to platelet-derived growth factor (PDGF). Imperatorin (Imp), iso-Imperatorin (iso Imp) and 6-(α,α-phenylacetylpiperazinyl)phenyl-5-methyl-4,5-dihydro-3 (2H)-pyridazinone (PMDP) did not affect the releasing of PDGF from IL-1α stimulated BCMEC, but inhibited the promotion of PDGF on the proliferation of BCMSMC. We concluded that the promotion of IL-1α on the proliferation of BCMSMC should be mediated by some growth factors, such as PDGF.