Rabbit Anti-Human TGFBR1 (internal) Polyclonal antibody

Introduction: Fibroblast activation protein alpha (FAP) is a membrane-bound serine protease expressed by activated fibroblasts during wound healing in the skin. Expression of FAP after myocardial infarction (MI) and potential effects on cardiac wound healing are largely unknown. Methods: MI was induced in rats and FAP expression was analyzed at 3, 7 and 28 days post-MI by microarray, Western blot and immunohistochemistry. In human hearts after MI, a FAP fibroblast population was identified, and characterized by immunohistochemistry for prolyl-4-hydroxylase beta, alpha-smooth muscle actin, Thy-1 and vimentin. Signaling pathways leading to FAP expression were studied in human cardiac fibroblasts by Western blot and ELISA using TGF beta(1), TGF-beta type I-receptor (TGFbR1)-inhibitor SB431542 or the MAPK-inhibitor U0126 as well as siRNA targeting SMAD2 and SMAD3. Finally, fibroblasts were assayed for FAP-dependent migration (modified Boyden-chamber), proliferation (BrdU-assay) and gelatinolytic activity by gelatin zymography. Results: In rats, FAP expression was increased after MI especially in the pen-infarct area peaking at 7 days post-MI. Co-localization analysis identified the majority of FAP(+) cells as activated proto-myofibroblasts and myofibroblasts. Concordantly, FAP(+) fibroblasts were abundant in ischemic tissue of human hearts after MI, but not in healthy control hearts. In vitro, FAP was induced by TGF beta(1) via the canonical SMAD2/SMAD3 pathway. Depletion of FAP in fibroblasts reduced migratory capacity, while proliferation was not affected. Gelatin zymography revealed gelatinase activity by fibroblast-derived FAP. Conclusion: In this study, we show for the first time the expression of FAP in activated fibroblasts after MI and its activation by TGF beta(1). Effects of FAP on fibroblast migration and gelatinolytic activity indicate a potential role in cardiac wound healing and remodeling. (C) 2015 Elsevier Ltd. All rights reserved.

The transforming growth factor (TGF)- is a potent growth inhibitor primarily responsible for cell growth, differentiation, and apoptosis, and frequently perturbed during development of tumors, including gastric cancer. TGF- receptor type I (TGFR1) may be a modifier of cancer risk by constitutively decreasing the TGF- inhibitory signals during early tumorigenesis and increasing the TGF- signals in tumor progression. In this study, we hypothesized that genetic variants of TGFBR1 may influence the risk of gastric cancer. We conducted a two-stage case-control study of gastric cancer, including 650 cases and 683 controls in the first stage and 484 cases and 348 controls in the second stage, and genotyped five tagging single nucleotide polymorphisms (SNPs) to represent common variants in the whole TGFBR1 gene. In the first stage, two SNPs rs6478974 and rs10512263 were found to be potentially associated with risk of gastric cancer (P=3.35x10(-3) for rs6478974 AT vs. TT and P=0.033 for rs10512263 CT vs. TT), which were further confirmed in the second stage with similar effects (P=0.144 and 0.049, respectively). After combining the two stages, we found that these two SNPs were associated with a significantly increased risk of gastric cancer in dominant models [adjusted odds ratio (OR)=1.36, 95% confidence interval (CI): 1.14-1.63 for rs6478974 AT/AA vs. TT; adjusted OR=1.26, 95% CI: 1.05-1.50 for rs10512263 CT/CC vs. TT] or additive model (adjusted OR=1.23, 95% CI: 1.08-1.40 for rs6478974). These findings indicate that TGFBR1 polymorphisms may be implicated with the development of gastric cancer in Han-Chinese population. (c) 2012 Wiley Periodicals, Inc.