Uncovering the profile of mutations of transforming growth factor beta-induced gene in Chinese corneal dystrophy patients

AIM： To uncover the mutations profile of transforming growth factor beta-induced （TGFBI） gene in Chinese corneal dystrophy patients and further investigate the characteristics of genotype-phenotype correlations. METHODS： Forty-two subjects （6 unrelated families including 15 patients and 8 unaffected members, and 19 sporadic patients） of Chinese origin were subjected to phenotypic and genotypic characterization. The corneal phenotypes of patients were documented by slit lamp photography. Mutation screening of the coding regions of TGFBI was performed by direct sequencing. RESULTS： We detected four corneal dystrophy types. The most frequent phenotypes were granular corneal dystrophy （GCD） （including 3 families and 8 sporadic patients） and lattice corneal dystrophy （LCD） （including 2 families and 9 sporadic patients）. The next phenotypes were corneal dystrophy of Bowman layer （CDB） （1 family and 1 sporadic patient） and epithelial basement membrane dystrophy （EBMD） （1 sporadic patient）. Six distinct mutations responsible for TGFBI corneal dystrophies were identified in 30 individuals with corneal dystrophies. Those were, p.R124H mutation in 1 family and 2 sporadic patients with GCD, p.R555W mutation in 2 families and 3 sporadic patients with GCD, p.R124C mutation in 2 families and 7 sporadic patients with LCD, p.A620D mutation in 1 sporadic patient with LCD, p.H626R mutation in 1 sporadic patient with LCD, and p.R555Q in 1 family and 1 sporadic patient with CDB. No mutation was detected in the remaining 3 atypical GCD patients and 1 EBMD patient, CONCLUSION： GCD and LCD are the most frequent phenotypes in Chinese population. R555W was the most common mutation for GCD; R124C was the most common mutation for LCD, Our findings extend the mutational spectrum of TFGBI , and this is the extensively delineated TGFBI mutation profile associated with the various corneal dystrophies in the Chinese population.

Two mutations in the transforming growth factor beta-induced gene associated with familial Lattice corneal dystrophy

AIM：To report a phenotypic variant pedigree of lattice corneal dystrophy（LCD）associated with two mutations,R124C and A546 D,in the transforming growth factor betainduced gene（TGFBI）.METHODS：A detailed ocular examination was taken for all participants of a LCD family. Peripheral blood leukocytes from each participant were extracted to obtain the DNA. Polymerase chain reaction（PCR）of all seventeen exons of TGFBI gene was performed. The products were sequenced and analyzed. Histological examination was carried out after a penetrating keratoplasty from the right eye of proband. RESULTS：Genetic analysis showed that the proband and all 6 affected individuals harbored both a heterozygous CGC to TGC mutation at codon 124 and a heterozygous GCC to GAC mutation at codon 546 of TGFBI. None of the 100 control subjects and unaffected family members was positive for these two mutations. Ocular examination displayed multiple refractile lattice-like opacities in anterior stroma of the central cornea and small granular deposits in the peripheral cornea. The deposits were stained positively with Congo red indicating be amyloid in nature and situated mainly in the anterior and middle stroma. CONCLUSION：We observed a novel LCD family which carried two pathogenic mutations（R124C and A546D）in the TGFBI gene. The phenotypic features were apparently different from those associated with corresponding single mutations. The result reveals that although the definite mutation is the most important genetic cause of the disease,some different modifier alleles may influence the phenotype.

The involvement of p38 MAPK in transforming growth factor β1-induced apoptosis in murine hepatocytes

We reported in this manuscript that TGF-beta1 induces apoptosis in AML12 murine hepatocytes, which is associated with the activation of p38 MAPK signaling pathway. SB202190, a specific inhibitor of p38 MAPK, strongly inhibited the TGF-beta1-induced apoptosis and PAI-1 promoter activity. Treatment of cells with TGF-beta1 activates p38. Furthermore, over-expression of dominant negative mutant p38 also reduced the TGF-beta1-induced apoptosis. The data indicate that the activation of p38 is involved in TGF-beta1-mediated gene expression and apoptosis.

Molecular Tissue Engineering: Applications for Modulation of Mesenchymal Stem Cells Proliferation by Transforming Growth Factor β_1 Gene Transfer

The effect of transforming growth factor β 1 (TGF β 1 ) gene transfection on the proliferation of bone marrow derived mesenchymal stem cells (MSC S ) and the mechanism was investigated to provide basis for accelerating articular cartilage repairing using molecular tissue engineering technology. TGF β 1 gene at different doses was transduced into the rat bone marrow derived MSCs to examine the effects of TGF β 1 gene transfection on MSCs DNA synthesis, cell cycle kinetics and the expression of proliferating cell nuclear antigen (PCNA). The results showed that 3 μl lipofectamine mediated 1 μg TGF β 1 gene transfection could effectively promote the proliferation of MSCs best; Under this condition (DNA/Lipofectamine=1μg/3μl), flow cytometry and immunohistochemical analyses revealed a significant increase in the 3 H incorporation, DNA content in S phase and the expression of PCNA. Transfection of gene encoding TGF β 1 could induce the cells at G0/G1 phase to S1 phase, modulate the replication of DNA through the enhancement of the PCNA expression, increase the content of DNA at S1 phase and promote the proliferation of MSCs. This new molecular tissue engineering approach could be of potential benefit to enhance the repair of damaged articular cartilage, especially those caused by degenerative joint diseases.

Osteogenic Potential of Cultured Bone Marrow Stromal Cells Transfected with Transforming Growth Factor β_1 Gene in vitro

To study the osteogenic potential of cultured bone marrow stromal cells transfected with transforming growth factor β 1 gene in vitro , cultured BMSCs were transfected with the complexes of pcDNA 3 TGF β 1 and Lipofectamine Reagent in vitro . The cell proliferation was detected by MTT method and the morphological features of transfected BMSCs was observed. ALP stains and PNP method were used to measure ALP activity. In addition, the collagen type Ⅰ propeptides and mineralized matrixes were examined by immunohistochemical staining and tetracycline fluorescence labeling respectively. The morphological and biological characters of the transfected BMSCs were similar to those of osteoblasts and the cell proliferation was promoted. The cell layer displayed strong positive reaction for ALP stains and immunohistochemical staining. ALP activity and collagen type Ⅰ expression increased remarkably after transfection. Mineralized matrixes formed earlier and more in transfected BMSCs as compared with control group. It is concluded that transfecting with TGF β 1 gene could promote the osteogenic potential of cultured BMSCs.

Cloning and sequencing of the fourth exon of transforming growth factor α gene

Using normal brain cell geneomic DNA as a template,transforming growth factor(TGFa)-IV exon gene was amplified by polymerase chain reaction(PCR). The sequence of amplified fragment was analysed with a DNA sequencing kit.The results showed that the cloned fragment is proved to be the TGFa-IV exon gene.

Study of Rat Osteoblasts Transfected by Transforming Growth Factorβ_(1)Gene

Summary:In order to investigate the effect of TGFβ_(1) gene transfer on the biological characteristics,the effects of gene transfer and supernatant of transfected osteoblasts on the proliferation and ALP activity of osteoblasts were detected by ^(3)H-TdR and MTT.Our results showed that TGFβ_(1) gene transfer had no effect on the biological characteristics and the activated supernatant of transfected osteoblasts stimulated proliferation and inhibited ALP activity of osteoblasts.TGFβ_(1) gene transfer could promote the expression of TGFβ_(1) and the biological characteristics of transfected osteoblasts were stable,which might be helpful for gene therapy of bone defects in vivo.

Cloning and Expression of Rat Transforming Growth Factor β1 cDNA in Osteoblasts

Summary: Rat transforming growth factor β1 (rTGFβ1) cDNA from rat lymphocytes was cloned by RT-PCR and inserted into pcDNA3 to construct an eukaryotic expression vector, which was named pcDNA3-TGFβ1. The cloned gene was confirmed to code rat TGFβ1 by restriction enzyme analysis. pcDNA3-TGFβ1 plasmid was transfected into rat osteoblasts by using liposome-mediated gene transfer technique and the expression of TGFβ1 was detected by using irnmunohistochemical staining assay. It was found that the rat TGFβ1 expression product was obviously detectable in the transfected osteoblasts in 48 h. High expression of TGFβ1 was obtained in the rat osteoblasts in which the constructed TGFβ1 expression vector was transfected.

Expression of Transforming Growth Factor β_(1) in Mesenchymal Stem Cells: Potential Utility in Molecular Tissue Engineering for Osteochondral Repair

The feasibility of using gene therapy to treat full-thickness articular cartilage defects was investigated with respect to the transfection and expression of exogenous transforming growth factor(TGF)-β_(1)genes in bone marrow-derived mesenchymal stem cells(MSCs)in vitro.The full-length rat TGF-β_(1)cDNA was transfected to MSCs mediated by lipofectamine and then selected with G418,a synthetic neomycin analog.The transient and stable expression of TGF-β_(1)by MSCs was detected by using immunohistochemical staining.The lipofectamine-mediated gene therapy efficiently transfected MSCs in vitro with the TGF-β_(1)gene causing a marked up-regulation in TGF-β_(1)expression as compared with the vector-transfected control groups,and the increased expression persisted for at least 4 weeks after selected with G418.It was suggested that bone marrow-derived MSCs were susceptible to in vitro lipofectamine mediated TGF-β_(1)gene transfer and that transgene expression persisted for at least 4 weeks.Having successfully combined the existing techniques of tissue engineering with the novel possibilities offered by modern gene transfer technology,an innovative concept,i.e.molecular tissue engineering,are put forward for the first time.As a new branch of tissue engineering,it represents both a new area and an important trend in research.Using this technique,we have a new powerful tool with which:(1)to modify the functional biology of articular tissue repair along defined pathways of growth and differentiation and(2)to affect a better repair of full-thickness articular cartilage defects that occur as a result of injury and osteoarthritis.

Expression of TGF-β1 in Placenta of the Patients with Pregnancy-induced Hypertension and Its relationship with Serum VCAM-1

The expression of transforming growth factor-β1 (TGF-β1) in placental tissue of pregnancy-induced hypertension (PIH) and the relationship between the level of expression of TGF-β1 and the amount of vascular cell adhesion molecule-1 (VCAM-1) in serum was studied. Immunohistochemistry ABC was used to detect the expression and distribution of TGF-β1 in placental tissues in 40 PIH women and 20 normal pregnancy women. High resolution pathological image analysis system was used to determine the quality of TGF-β1. The VCAM-1 in serum was examined by enzyme linked immunoabsorbent assay (ELISA). The results showed that TGF-β1 could be express in syncytiotrophoblast. The levels of TGF-β1 expression in placental tissues of the patients with moderate and severe PIH were significantly higher (P<0.05), while the serum VCAM-1 was significantly lower than in normal group (P<0.01). There was a significant positive correlation between the expression of TGF-β1 in placental tissues and the serum VCAM-1 (r=0.969, P<0.01). It was concluded that the level of TGF-β1 expression in PIH was increased and was positively correlated with the amount of serum VCAM-1, indicating that they might be involved in the pathogenesis of PIH.

EGFR inhibitors sensitize non-small cell lung cancer cells to TRAIL-induced apoptosis

Apoptosis induced by tumor necrosis factor-related apoptosis-inducing ligand(TRAIL) can be regulated by the epidermal growth factor(EGF) signaling pathway.In this study,recombinant adenoviral vectors that encode TRAIL gene from the hTERT/RGD promoter(AdTRAIL) was combined with drugs including gefitinib,elotinib,and cetuximab that inhibit EGFR and the EGF signaling pathway in non-small cell lung cancer(NSCLC) cell lines to investigate their antitumor activity.In vitro,compared to single reagent,AdTRAIL combined with EGFR inhibitors reduced proliferation and enhanced apoptosis in H460,A549,and SW1573 cell lines.Western blot results suggested that these effects were relative to up-regulation of pro-apoptosis protein BAX and down-regulation of p-AKT.In vivo,AdTRAIL combined with cetuximab resulted in a significant growth reduction in H460 xenografts without damage to the main organs of nude mice.Histological examination and TUNEL analyses of xenografts showed that cetuximab enhanced cell apoptosis induced by AdTRAIL.These results indicate that EGFR inhibitors enhanced AdTRAIL anti-tumor activity in NSCLC cell lines and that inhibiting the AKT pathway played an important role in this enhancement.

Effects of IGF-Ⅱand TGF-β1 on invasiveness of placental trophoblast cells in patients with pregnancy-induced hypertension syndrome

Objective: This study was to investigate the invasiveness of pregnancy-induced hypertension (PIH) trophoblast cells and evaluate the effects of IGF-Ⅱand TGF-β1 on cytotrophoblast invasion.Methods: Cytotrophoblast cells from normal and PIH placenta were separated and purified. Cytotrophoblast invasiveness of normal and PIH placenta was measured by in vitro invasion assay. Effects of IGF-Ⅱand TGF-β1 on cytotrophoblast invasion were also studied.Results: In PIH group, cytotrophoblast invasiveness was dramatically decreased. In normal group, trophoblast invasiveness was significantly enhanced by IGF-Ⅱ but inhibited by TGF-β1. Neither IGF-Ⅱ nor TGF-β1 had statistically significant effects on PIH trophoblast invasion.Conclusions: PIH cytotrophoblast invasiveness dramatically decreases as compared to the normal level. IGF-Ⅱand TGF-β1 may play an important role in shallow trophoblast invasion on PIH.

获得性异位骨化的分子生物学机制

背景:异位骨化是一个动态发展的过程,临床中不同亚型的异位骨化具有不同病因或诱导因素,但在异位骨化中后期进展阶段又表现出相似的病理过程,其中由于创伤等因素引起的获得性异位骨化具有较高的发病率。目的:对近年获得性异位骨化发生发展相关分子生物学机制研究进行综述。方法:以“分子生物学,异位骨化,机制”为检索词在中国知网、万方医学数据库进行检索,以“molecular biological,heterotopic ossification,mechanisms”为检索词分别在PubMed、Embase、Web of Science及Google Scholar数据库进行检索,检索时限为2016年1月至2022年8月,并根据获得文献进行补充检索,对所得文献进行筛选,最终纳入131篇文献进行综述分析。结果与结论:①获得性异位骨化的发生和发展是一个动态的过程,具有一定的隐匿性,因此该疾病的诊疗有一定的困难。②文章通过综述国内外相关文献,发现获得性异位骨化涉及骨形态发生蛋白、转化生长因子β、Hedgehog、Wnt及mTOR共5条主要信号通路,同时在局部微环境中涉及到Runx2、血管内皮生长因子、缺氧诱导因子、成纤维细胞生长因子及Sox9共5项核心枢纽因子,核心机制可能是不同信号通路之间的相互作用,影响机体成骨细胞前体细胞、成骨细胞微环境以及与此相关的细胞因子,进而影响机体骨代谢并导致获得性异位骨化的发生。③未来可以以异位骨化相关单细胞的成骨内稳态为研究方向,以成骨细胞前体细胞-成骨微环境-信号通路及细胞因子作为研究要素,探索各部分要素在不同时空条件下的特征,比较不同种类、不同个体细胞成骨内稳态异同,从整体视角观察异位骨化分子信号网络调控机制,有利于未来临床防治异位骨化新方法的探究。④以中医药及靶向治疗为代表的治疗方法是近年的研究热点,如何将中医药与体内成骨稳态联系,并与靶向治疗相结合,也是未来研究方向之一。⑤目前获得性异位骨化的研究仍多限于基础实验研究,临床防治方法仍存在疗效不确切及不良反应明显等缺陷,相关靶向防治药物临床应用安全性及有效性仍有待验证,如何以基础实验研究为基础,结合发生发展机制,为临床防治提供新方向将是未来研究的重点。

补肾活血汤调控宫腔粘连大鼠内膜纤维化进程的作用机制研究

目的:探究微RNA-655(miR-665)/冷诱导核糖核酸结合蛋白(CIRBP)在宫腔粘连(IUA)子宫内膜纤维化中的作用以及补肾活血汤对其的调控作用。方法:使用miRNA靶基因数据库(TargetScan)分析miR-665和CIRBP的结合情况;通过实时定量聚合酶链反应(qRT-PCR)和蛋白免疫印迹技术检测细胞和动物模型中miR-665和CIRBP的转录和表达水平;借助双荧光素酶报告系统和构建过表达载体验证miR-665和CIRBP之间相互调控的作用,以及补肾活血汤对miR-665/CIRBP的调控作用;利用酶联免疫吸附测定(ELISA)和苏木精-伊红(HE)染色检测大鼠宫腔粘连模型中相关因子水平和组织病变程度。结果:在宫腔粘连模型大鼠组织中,CIRBP转录水平显著上升,而miR-665转录水平显著下降。体外实验显示,miR-665模拟物可降低子宫内膜基质细胞中CIRBP的表达水平。此外,补肾活血汤能够降低宫腔粘连的大鼠模型血清中转化生长因子β_(1)(TGF-β_(1))、雌二醇(E_(2))和肿瘤坏死因子-α(TNF-α)的水平。补肾活血汤可以提高miR-665的转录水平并降低CIRBP的表达水平,并减轻大鼠子宫内膜组织的病变程度。结论:补肾活血汤通过调控miR-665/CIRBP途径来减轻宫腔粘连大鼠子宫内膜纤维化程度,为宫腔粘连的治疗提供了新的策略和方向。

沙参麦冬汤干预小细胞肺癌患者放射性肺损伤的作用与机制

目的探讨小细胞肺癌(small cell lung cancer,SCLC)合并放射性肺损伤患者应用沙参麦冬汤疗法对其血清转化生长因子-β(transforming growth factor-β,TGF-β)/Smad信号通路相关因子的影响及作用机制。方法选取接受放射治疗的104例SCLC合并放射性肺损伤患者,采用随机数字表法分为沙参麦冬汤干预组及常规治疗组,每组52例。常规治疗组予以常规西药治疗,沙参麦冬汤干预组在常规治疗组治疗的基础上加用沙参麦冬汤剂。观察2组的临床疗效,对比2组患者治疗前后的TGF-β、肿瘤坏死因子-α(tumor necrosis factor,TNF-α)和白细胞介素-6(interleukin-6,IL-6)水平,对比2组治疗前后身体机能状态量表(karnofsky performance scale,KPS)评分和临床-影像-生理(clinical-radiologicand physiological scale,CRP)评分,分析SCLC合并放射性肺损伤患者CRP评分与KPS评分的相关性。结果沙参麦冬汤干预组的临床治疗总有效率较常规治疗组明显升高(P<0.05);治疗后,2组血清TGF-β、TNF-α和IL-6水平均明显降低,且沙参麦冬汤干预组各指标较常规治疗组均明显降低(均P<0.05);2组KPS评分均明显升高,且沙参麦冬汤干预组高于常规治疗组(P<0.05);2组CRP评分均明显降低,且沙参麦冬汤干预组较常规治疗组明显降低(P<0.05);Pearson相关系数分析结果显示,SCLC合并放射性肺损伤患者CRP评分与KPS评分呈明显负相关(P<0.05)。结论沙参麦冬汤干预疗法对改善SCLC患者放射性肺损伤疗效显著,有助于降低患者血清TGF-β、TNF-α和IL-6水平,对抑制机体炎性反应、改善患者生活质量等具有积极作用。

促血管生成因子在支气管肺发育不良中的研究进展

随着医疗技术的不断进步,极早产儿存活率不断提高,支气管肺发育不良的发生率也随之升高。肺血管生成受损、肺泡发育停滞、细胞外基质改变是支气管肺发育不良的主要特征。促血管生成因子水平变化对维持正常肺血管生成及肺泡发育具有关键作用,如血管内皮生长因子、血管生成素、血小板源性生长因子、肝细胞生长因子等。上述促血管生成因子均与支气管肺发育不良密切相关,在该病的临床防治中具有良好的发展前景。

Transforming Growth Factor-beta I Involved in the Pathogenesis of Endometriosis through Regulating Expression of Vascular Endothelial Growth Factor under Hypoxia

Background： Endometriosis （EMs） is a common gynecological disorder characterized by endometrial-like tissue outside the uterus. Hypoxia induces the expression of many important downstream genes to regulate the implantation, survival, and maintenance ofectopic endometriotic lesions. Transtbrming growth factor-beta I （TGF-β1） plays a major role in the etiology of EMs. We aimed to determine whether TGF-β1 affects EMs development and progression and its related mechanisms in hypoxic conditions. Methods： Endometrial tissue was obtained from women with or without EMs undergoing surgery from October, 2015 to October, 2016. Endometrial cells were cultured and then exposed to hypoxia and TGF-β1 or TGF-β1 inhibitors. The messenger RNA （mRNA） and protein expression levels ofTGF-β1, vascular endothelial growth fhctor （VEGF）, and hypoxia-inducible fhctor-Ic~ （HIF-β1） were measured. A DuaI-Luciferase Reporter Assay was used to examine the effect ofTGF-[31 and hypoxia on a VEGF promoter construct. Student＇s t-test was pertbrmed/br comparison among groups （one-sided or two-sided） and a value ofP 〈 0.05 was considered statistically significant. Results： TGF-β1, VEGF, HIF-β1 mRNA, and protein expression were significantly higher in EMs tissue than that in normal endometrial tissue （t = 2.16, P = 0.042）. EMs primary cultured cells exposed to hypoxia expressed 43.8% higher VEGF mRNA and protein （t = 6.84, P - 0.023）. VEGF mRNA levels increased 12.5% in response to TGF-β1, whereas the combined treatment of hypoxia/TGF-β1 resulted in a much higher production （87.5% increases） of VEGF. The luciferase activity of the VEGF promoter construct was increased in the presence of either TGF-β1 （2.6-fold, t = 6.08, P = 0.032） or hypoxia （11.2-fold, t = 32.70, P 〈 0.001 ）, whereas the simultaneous presence of both stimuli resulted in a significant cooperative effect （ 18.5-fold, t = 33.50, P 〈 0.001 ）. Conclusions： The data support the hypothesis that TGF-β1 is involved in the pathogenesis of EMs through regulating VEGF expression. An additive effect of TGF-[31 and hypoxia is taking place at the transcriptional level.

Association of Chinese Medicine Constitution Susceptibility to Diabetic Nephropathy and Transforming Growth Factor-β1(T869C)Gene Polymorphism

Objective：To explore the association of Chinese medicine constitution susceptibility to diabetic nephropathy（DN） and transforming growth factor（TGF）-β1（T869C） gene polymorphism.Methods：TGF-β1 gene polymorphism detected with polymerase chain reaction-restriction fragment length polymorphism（PCRRFLP） was screened for 180 DN cases and 180 type 2 diabetic mellitus（T2DM） cases without combined DN. Patients with DN were surveyed epidemiologically with constitution in the Chinese medicine questionnaire （CCMQ）.Binary logistic regression analysis was utilized to study the correlation between nine types of Chinese medicine constitution and TGF-β1（T869C） gene polymorphisms.Results：The DN group has a higher frequency of TGF-β1（T869C） gene polymorphism than the T2DM group,and CC/CT genotypes than the T2DM group[CC,CT,TT（DN group）：88,87,5（cases） versus（T2DM group） 71,73,36（cases）,P0.05].The phlegm-dampness constitution,damp-heat constitution,and blood stasis constitution have correlations with TGF-β1 （T869C） gene polymorphism.Conclusion：Chinese medicine constitutions were associated with TGF-β1（T869C） gene polymorphism,a potential predictor of susceptibility to DN in T2DM patients.

Effects of single nucleotide polymorphisms 869 T/C and 915 G/C in the exon 1 locus of transforming growth factor-β1 gene on chronic obstructive pulmonary disease susceptibility in Chinese

Background The main risk factor for chronic obstructive pulmonary disease （COPD） is cigarette smoking. However, only 10%-20% of chronic heavy smokers develop systematic COPD. We hypothesized that the inheritance of gene polymorphisms could influence the development of COPD, which was investigated by studying two single nucleotide polymorphisms （SNP） in exon 1 of the transforming growth factor-β1 （TGF-β1） gene. Methods We enrolled 219 patients with COPD as the research group and 148 healthy people as the control group, all of whom were Chinese Han people. The polymorphisms of the TGF-β1 gene, 869T/C and 915G/C, were analyzed using the method of amplification refractory mutation system-polymerase chain reaction （ARMS-PCR）. Results The occurrence of the TGF-β1 gene 869T/C polymorphism in patients with COPD was significantly different from the control group （P 〈0.05）, in which the relative risk of this disease increased in cases who had the C allele （OR： 1.131, 95% CI： 1.101-1.539）. There was no increased frequency of TGF-β1 915G/C gene in COPD patients compared with control subjects （P 〉0.05）. Conclusions The polymorphism 869T/C in TGF-β1 gene has a significant association with disease occurrence in COPD patients and the C allele might be a risk factor. The homozygous wild-type CC of 869T/C on TGFβ1 could be a predisposing factor in COPD and those who carry the C allele might have particularly susceptibility to developing COPD.

Idiopathic pulmonary fibrosis in relation to gene polymorphisms of transforming growth factor-β1 and plasminogen activator inhibitor 1

Background Idiopathic pulmonary fibrosis （IPF） is a progressive and lethal fibrotic lung disease of unknown etiology. Host susceptibility or genetic factors may be important for the predisposition to it. Transforming growth factor-β1 （TGF-β1 a potent profibrotic cytokine） and plasminogen activator inhibitor 1 （PAl-1） play important roles in the development of pulmonary fibrosis. The objective of the study was to investigate the association between the gene polymorphisms of TGF-β1 869 T〉C and PAl-1 4G/5G and the susceptibility to IPF in Han ethnicity. Methods Polymerase chain reaction （PCR） and restriction fragment length polymorphism were performed to analyse the gene polymorphisms of TGF-β1 in 869T〉C and PAl-1 4G/5G in 85 IPF patients and 85 healthy controls matched in age, gender, race and smoker status. Results There was a significant difference in 869T〉C genotype distribution of TGF-β1 between IPF cases and controls, a significant negative association between TC genotype and the development of IPF （OR=0.508, 95% CI： 0.275-0.941） and a positive association between CC genotype and the development of IPF （OR=1.967, 95% CI： 1.063-3.641）. There was a significant positive association between PAl-1 5G/5G genotype and the development of IPF （OR=0.418, 95% CI： 0.193-0.904）. Conclusions Gene polymorphisms of TGF-β1 in 869T〉Cand PAl-1 4G/5G may affect the susceptibility to IPF in Han ethnicity. Further investigations are needed to confirm these findings and assess their biological significance in the development of the disease in this ethnic population.