Objective: To analyze and compare the expression pattern of the transforming growth factor-β1(TGF-β1) and its type I receptor (TGF-β RI ) in nounal human skin and various phases of post-burn hypertrophic scars (HTS...Objective: To analyze and compare the expression pattern of the transforming growth factor-β1(TGF-β1) and its type I receptor (TGF-β RI ) in nounal human skin and various phases of post-burn hypertrophic scars (HTS). Method: The immunohistochemical ABC method was employed. Results: In nounal human skin, no evident immunoreactivity of TGF-β1 and TGF-β R I was observed. In activation phase of post-burn HTS, TGF-β R I and TGF-β1 were highly expressed in most dermal fibroblasts which seemed to be the same subset. However, in remission phase, no staining was seen in der mal fibroblasts. Conclusion: The formation of all may involve the increase of TGF-β responsiveness in fibroblasts The ac cumulation at the wound site and failure of apoptosis of over-resposive fibroblasts may contribute to the formation of HTS.展开更多
The effects of transforming growth factor-β1 （TGF-β1） are currently controversial. Whether TGF-β1 promotes or inhibits revascularization under different conditions remains poorly understood. Based on previous stu...The effects of transforming growth factor-β1 （TGF-β1） are currently controversial. Whether TGF-β1 promotes or inhibits revascularization under different conditions remains poorly understood. Based on previous studies, the current experiment established rat models of cerebral ischemia and reperfusion injury （IRI）, and demonstrated that pathological and functional damage was also increased after IRI. The most serious damage was observed at 3 days after reperfusion, at which time microvascular density fell to its lowest level. Soon afterwards, microvascular density increased, new collateral circulation was gradually established at 4 to 7 days after reperfusion, and pathological damage and neurological deficits were improved. TGF-β1, activin receptor-like kinase 5 （ALK5） mRNA and protein expression levels increased gradually over time. In contrast, ALK1 mRNA and protein expression decreased over the same period. A significant negative correlation was detected between microvascular density and expression of the ALK5 gene transcript. There was no correlation between microvascular density and ALK1 gene transcriptional expression following cerebral IRI in a rat model. These findings suggest that ALK5, rather than ALK1, is the critical receptor in the TGF-β1 signal pathways after cerebral IRI.展开更多
AIM:To investigate the role of genetic polymorphisms in the progression of hepatic fibrosis in hereditary haemochromatosis.METHODS:A cohort of 245 well-characterised C282Y homozygous patients with haemochromatosis was...AIM:To investigate the role of genetic polymorphisms in the progression of hepatic fibrosis in hereditary haemochromatosis.METHODS:A cohort of 245 well-characterised C282Y homozygous patients with haemochromatosis was studied,with all subjects having liver biopsy data and DNA available for testing.This study assessed the association of eight single nucleotide polymorphisms(SNPs)in a total of six genes including toll-like receptor 4(TLR4),transforming growth factor-beta(TGF-β),oxoguanine DNA glycosylase,monocyte chemoattractant protein 1,chemokine C-C motif receptor 2 and interleukin-10 with liver disease severity.Genotyping was performed using high resolution melt analysis and sequencing.The results were analysed in relation to the stage of hepatic fibrosis in multivariate analysis incorporating other cofactors including alcohol consumption and hepatic iron concentration.RESULTS:There were significant associations between the cofactors of male gender(P=0.0001),increasing age(P=0.006),alcohol consumption(P=0.0001),steatosis(P=0.03),hepatic iron concentration(P<0.0001)and the presence of hepatic fibrosis.Of the candidate gene polymorphisms studied,none showed a significant association with hepatic fibrosis in univariate or multivariate analysis incorporating cofactors.We also specifically studied patients with hepatic iron loading above threshold levels for cirrhosis and compared the genetic polymorphisms between those with no fibrosis vs cirrhosis however there was no significant effect from any of the candidate genes studied.Importantly,in this large,well characterised cohort of patients there was no association between SNPs for TGF-βor TLR4and the presence of fibrosis,cirrhosis or increasing fibrosis stage in multivariate analysis.CONCLUSION:In our large,well characterised group of haemochromatosis subjects we did not demonstrate any relationship between candidate gene polymorphisms and hepatic fibrosis or cirrhosis.展开更多
OBJECTIVE To study the relationship among microsatellite instability （MSI）, frameshift mutations （FM） of the transforming growth factor β receptor Ⅱ （TGF β R Ⅱ）, methylation state of the hMLH1 promoter and h...OBJECTIVE To study the relationship among microsatellite instability （MSI）, frameshift mutations （FM） of the transforming growth factor β receptor Ⅱ （TGF β R Ⅱ）, methylation state of the hMLH1 promoter and hMLH1 protein expression level in gastric cancers, and to explore their relationship to gastric carcinogenesis. METHODS DNA was isolated from 101 gastric specimens and 5 microsatellite loci were detected. PCR, electrophoresis on denatured polyacrylamide gels and silver staining were performed to detect the MSI. The FMs of TGFβR Ⅱ were also screened with the same method. HMLH1 methylation was analyzed by methylation specific PCR （MSP） and sequencing. HMLH1 protein expression was detected using immunohistochemistry. RESULTS The incidence of MSIs was 53.7% and 0% in the cancers and normal tissues, respectively, with the frequency of MSIs being significantly higher in the gastric cancers compared to the normal gastric tissues （P〈0.05）. The frequency of hMLH1 methylation was 41.5%（17/41） in the gastric cancers and 0%（0/60） in the normal group. Decreased hMLH1 expression was observed in 94.1%（16/17） of cases exhibiting methylation. FMs of TGFβR Ⅱ were identified in 5 （62.5%） of the 8 samples with MSIH. In contrast, FMs were not found in MSI-L or microsatellite stable （MSS） cases. CONCLUSION MSIs and FMs of TGFβR Ⅱ may play an important role in gastric carcinogenesis. HMLH1 methylation is an important modification of the DNA which results in inactivation of hMLH1 and mismatch repair defects which lead to MSls and FMs of TGFβR Ⅱ.展开更多
Objective Ubiquitin-specific protease 4(USP4)facilitates the development of transforming growth factor-beta 1(TGF-β1)-induced epithelial-mesenchymal transition(EMT)in various cancer cells.Moreover,EMT of renal tubula...Objective Ubiquitin-specific protease 4(USP4)facilitates the development of transforming growth factor-beta 1(TGF-β1)-induced epithelial-mesenchymal transition(EMT)in various cancer cells.Moreover,EMT of renal tubular epithelial cells(RTECs)is required for the progression of renal interstitial fibrosis.However,the role of USP4 in EMT of RTECs remains unknown.The present study aimed to explore the effect of USP4 on the EMT of RTECs as well as the involved mechanism.Methods In established unilateral ureteral obstruction(UUO)rats and NRK-52E cells,immunohistochemistry and Western blot assays were performed.Results USP4 expression was increased significantly with obstruction time.In NRK-52E cells stimulated by TGF-β1,USP4 expression was increased in a time-dependent manner.In addition,USP4 silencing with specific siRNA indicated that USP4 protein was suppressed effectively.Meanwhile,USP4 siRNA treatment restored E-cadherin and weakened alpha smooth muscle actin(α-SMA)expression,indicating that USP4 may promote EMT.After treatment with USP4 siRNA and TGF-β1 for 24 h,the expression of TGF-β1 receptor type I(TβRI)was decreased.Conclusion USP4 promotes the EMT of RTECs through upregulating TβRI,thereby facilitating renal interstitial fibrosis.These findings may provide a potential target of USP4 in the treatment of renal fibrosis.展开更多
Objective: To detect the relations of c-erbB-2 onco-gene protein, epidermal growth factor receptor (EG-FR) and transforming growth factor-β1 (TGF-β1)to the progression or metastasis of pancreatic carci-noma.Methods:...Objective: To detect the relations of c-erbB-2 onco-gene protein, epidermal growth factor receptor (EG-FR) and transforming growth factor-β1 (TGF-β1)to the progression or metastasis of pancreatic carci-noma.Methods: Using streptavidinbiotin complex (SABC)method, c-erbB-2 oncongene protein, we examinedimmunohistochemically EGFR and TGF-β1 expres-sions in wax-tissue sections from 10 individuals withnormal pancreas (NP), 13 patients with chronic pan-creatitis (CP) and 36 patients with pancreatic ductaladenocarcinoma (PC).Results: The positive expression rates of c-cerbB-2oncogene protein, EGFR and TGF-β1 in the NP, CPand PC groups were 0, 0, 10%; 7.7%, 7.7%,7.7%; and 41.7%, 50.0%, 44.4%, respectively.The positive expression rates of the three specific pro-teins increased more significantly in the PC groupthan in the NP and CP groups (P【0.05). The indi-vidual expression of c-erbB-2, EGFR and TGF-β1was not related to the age and sex of the patients aswell as the site, size and histopathological grade oftumors (P】0.05), but to the clinical stage of tumors(P【0.01). The coexpression rate of the three pro-teins was 27.8 % (10/36). This coexpression in thePC group was correlated with the histopathologicalgrades and clinical stages of tumors (P【0.01).Conclusion: Detection of c-erbB-2 oncogene protein,EGFR, and TGF-β1 expressions in pancreatic tissueis helpful to judge the malignancy, progression, andmetastasis of PC.展开更多
文摘Objective: To analyze and compare the expression pattern of the transforming growth factor-β1(TGF-β1) and its type I receptor (TGF-β RI ) in nounal human skin and various phases of post-burn hypertrophic scars (HTS). Method: The immunohistochemical ABC method was employed. Results: In nounal human skin, no evident immunoreactivity of TGF-β1 and TGF-β R I was observed. In activation phase of post-burn HTS, TGF-β R I and TGF-β1 were highly expressed in most dermal fibroblasts which seemed to be the same subset. However, in remission phase, no staining was seen in der mal fibroblasts. Conclusion: The formation of all may involve the increase of TGF-β responsiveness in fibroblasts The ac cumulation at the wound site and failure of apoptosis of over-resposive fibroblasts may contribute to the formation of HTS.
基金a grant of Supportive Fund for Young Scientists from the Department of Science & Technology of Shandong Province, China, No. 2004BS03013
文摘The effects of transforming growth factor-β1 （TGF-β1） are currently controversial. Whether TGF-β1 promotes or inhibits revascularization under different conditions remains poorly understood. Based on previous studies, the current experiment established rat models of cerebral ischemia and reperfusion injury （IRI）, and demonstrated that pathological and functional damage was also increased after IRI. The most serious damage was observed at 3 days after reperfusion, at which time microvascular density fell to its lowest level. Soon afterwards, microvascular density increased, new collateral circulation was gradually established at 4 to 7 days after reperfusion, and pathological damage and neurological deficits were improved. TGF-β1, activin receptor-like kinase 5 （ALK5） mRNA and protein expression levels increased gradually over time. In contrast, ALK1 mRNA and protein expression decreased over the same period. A significant negative correlation was detected between microvascular density and expression of the ALK5 gene transcript. There was no correlation between microvascular density and ALK1 gene transcriptional expression following cerebral IRI in a rat model. These findings suggest that ALK5, rather than ALK1, is the critical receptor in the TGF-β1 signal pathways after cerebral IRI.
基金Supported by NHMRC Medical Postgraduate Scholarship and the Royal Brisbane and Women’s Hospital Research Foundation to Wood MJthe National Health and Medical Research Council(NHMRC)to Ramm GA and Powell LW+1 种基金the recipient of an NHMRC Senior Research Fellowship,1024672 to Subramaniam VNan NHMRC Senior Research Fellowship,No.552409 to Ramm GA
文摘AIM:To investigate the role of genetic polymorphisms in the progression of hepatic fibrosis in hereditary haemochromatosis.METHODS:A cohort of 245 well-characterised C282Y homozygous patients with haemochromatosis was studied,with all subjects having liver biopsy data and DNA available for testing.This study assessed the association of eight single nucleotide polymorphisms(SNPs)in a total of six genes including toll-like receptor 4(TLR4),transforming growth factor-beta(TGF-β),oxoguanine DNA glycosylase,monocyte chemoattractant protein 1,chemokine C-C motif receptor 2 and interleukin-10 with liver disease severity.Genotyping was performed using high resolution melt analysis and sequencing.The results were analysed in relation to the stage of hepatic fibrosis in multivariate analysis incorporating other cofactors including alcohol consumption and hepatic iron concentration.RESULTS:There were significant associations between the cofactors of male gender(P=0.0001),increasing age(P=0.006),alcohol consumption(P=0.0001),steatosis(P=0.03),hepatic iron concentration(P<0.0001)and the presence of hepatic fibrosis.Of the candidate gene polymorphisms studied,none showed a significant association with hepatic fibrosis in univariate or multivariate analysis incorporating cofactors.We also specifically studied patients with hepatic iron loading above threshold levels for cirrhosis and compared the genetic polymorphisms between those with no fibrosis vs cirrhosis however there was no significant effect from any of the candidate genes studied.Importantly,in this large,well characterised cohort of patients there was no association between SNPs for TGF-βor TLR4and the presence of fibrosis,cirrhosis or increasing fibrosis stage in multivariate analysis.CONCLUSION:In our large,well characterised group of haemochromatosis subjects we did not demonstrate any relationship between candidate gene polymorphisms and hepatic fibrosis or cirrhosis.
文摘OBJECTIVE To study the relationship among microsatellite instability （MSI）, frameshift mutations （FM） of the transforming growth factor β receptor Ⅱ （TGF β R Ⅱ）, methylation state of the hMLH1 promoter and hMLH1 protein expression level in gastric cancers, and to explore their relationship to gastric carcinogenesis. METHODS DNA was isolated from 101 gastric specimens and 5 microsatellite loci were detected. PCR, electrophoresis on denatured polyacrylamide gels and silver staining were performed to detect the MSI. The FMs of TGFβR Ⅱ were also screened with the same method. HMLH1 methylation was analyzed by methylation specific PCR （MSP） and sequencing. HMLH1 protein expression was detected using immunohistochemistry. RESULTS The incidence of MSIs was 53.7% and 0% in the cancers and normal tissues, respectively, with the frequency of MSIs being significantly higher in the gastric cancers compared to the normal gastric tissues （P〈0.05）. The frequency of hMLH1 methylation was 41.5%（17/41） in the gastric cancers and 0%（0/60） in the normal group. Decreased hMLH1 expression was observed in 94.1%（16/17） of cases exhibiting methylation. FMs of TGFβR Ⅱ were identified in 5 （62.5%） of the 8 samples with MSIH. In contrast, FMs were not found in MSI-L or microsatellite stable （MSS） cases. CONCLUSION MSIs and FMs of TGFβR Ⅱ may play an important role in gastric carcinogenesis. HMLH1 methylation is an important modification of the DNA which results in inactivation of hMLH1 and mismatch repair defects which lead to MSls and FMs of TGFβR Ⅱ.
文摘Objective Ubiquitin-specific protease 4(USP4)facilitates the development of transforming growth factor-beta 1(TGF-β1)-induced epithelial-mesenchymal transition(EMT)in various cancer cells.Moreover,EMT of renal tubular epithelial cells(RTECs)is required for the progression of renal interstitial fibrosis.However,the role of USP4 in EMT of RTECs remains unknown.The present study aimed to explore the effect of USP4 on the EMT of RTECs as well as the involved mechanism.Methods In established unilateral ureteral obstruction(UUO)rats and NRK-52E cells,immunohistochemistry and Western blot assays were performed.Results USP4 expression was increased significantly with obstruction time.In NRK-52E cells stimulated by TGF-β1,USP4 expression was increased in a time-dependent manner.In addition,USP4 silencing with specific siRNA indicated that USP4 protein was suppressed effectively.Meanwhile,USP4 siRNA treatment restored E-cadherin and weakened alpha smooth muscle actin(α-SMA)expression,indicating that USP4 may promote EMT.After treatment with USP4 siRNA and TGF-β1 for 24 h,the expression of TGF-β1 receptor type I(TβRI)was decreased.Conclusion USP4 promotes the EMT of RTECs through upregulating TβRI,thereby facilitating renal interstitial fibrosis.These findings may provide a potential target of USP4 in the treatment of renal fibrosis.
文摘Objective: To detect the relations of c-erbB-2 onco-gene protein, epidermal growth factor receptor (EG-FR) and transforming growth factor-β1 (TGF-β1)to the progression or metastasis of pancreatic carci-noma.Methods: Using streptavidinbiotin complex (SABC)method, c-erbB-2 oncongene protein, we examinedimmunohistochemically EGFR and TGF-β1 expres-sions in wax-tissue sections from 10 individuals withnormal pancreas (NP), 13 patients with chronic pan-creatitis (CP) and 36 patients with pancreatic ductaladenocarcinoma (PC).Results: The positive expression rates of c-cerbB-2oncogene protein, EGFR and TGF-β1 in the NP, CPand PC groups were 0, 0, 10%; 7.7%, 7.7%,7.7%; and 41.7%, 50.0%, 44.4%, respectively.The positive expression rates of the three specific pro-teins increased more significantly in the PC groupthan in the NP and CP groups (P【0.05). The indi-vidual expression of c-erbB-2, EGFR and TGF-β1was not related to the age and sex of the patients aswell as the site, size and histopathological grade oftumors (P】0.05), but to the clinical stage of tumors(P【0.01). The coexpression rate of the three pro-teins was 27.8 % (10/36). This coexpression in thePC group was correlated with the histopathologicalgrades and clinical stages of tumors (P【0.01).Conclusion: Detection of c-erbB-2 oncogene protein,EGFR, and TGF-β1 expressions in pancreatic tissueis helpful to judge the malignancy, progression, andmetastasis of PC.
