دورية أكاديمية
أعرض في EDS

TGF-β1 induces EMT reprogramming of porcine bladder urothelial cells into collagen producing fibroblasts-like cells in a Smad2/Smad3-dependent manner.

التفاصيل البيبلوغرافية
العنوان: TGF-β1 induces EMT reprogramming of porcine bladder urothelial cells into collagen producing fibroblasts-like cells in a Smad2/Smad3-dependent manner.
المؤلفون: Islam SS; Program in Developmental & Stem Cell Biology, The Hospital for Sick Children Research Institute, Toronto, ON, Canada, syed.islam@sickkids.ca., Mokhtari RB, El Hout Y, Azadi MA, Alauddin M, Yeger H, Farhat WA
المصدر: Journal of cell communication and signaling [J Cell Commun Signal] 2014 Mar; Vol. 8 (1), pp. 39-58. Date of Electronic Publication: 2013 Dec 12.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Springer Country of Publication: Netherlands NLM ID: 101308338 Publication Model: Print-Electronic Cited Medium: Print ISSN: 1873-9601 (Print) Linking ISSN: 18739601 NLM ISO Abbreviation: J Cell Commun Signal Subsets: PubMed not MEDLINE
أسماء مطبوعة: Original Publication: Dordrecht : Springer, 2007-
مستخلص: Activation of fibroblasts and their differentiation into myofibroblasts, excessive collagen production and fibrosis occurs in a number of bladder diseases. Similarly, conversion of epithelial cells into mesenchymal cells (EMT) has been shown to increase fibroblasts like cells. TGF-β1 can induce the EMT and the role of TGF-β1-induced EMT during bladder injury leading to fibrosis and possible organ failure is gaining increasing interest. Here we show that EMT and fibrosis in porcine bladder urothelial (UC) cells are Smad dependent. Fresh normal porcine bladder urothelial cells were grown in culture with or without TGF-β1 and EMT markers were assessed. TGF-β1 treatment induced changes in cellular morphology as depicted by a significant decrease in the expression of E-cadherin and corresponding increase in N-cadherin and α-SMA. We knocked down Smad2 and Smad3 by Smad specific siRNA. Downregulation of E-cadherin expression by TGF-β1 was Smad3-dependent, whereas N-cadherin and α-SMA were dependent on both Smad2 and Smad3. Connective tissue growth factor (CTGF/CCN2), matrix metalloproteinase-2 and -9 (MMP-2, MMP-9) has been shown to play important roles in the pathogenesis of fibrosis. Induction of these genes by TGF-β1 was found to be time dependent. Upregulation of CTGF/CCN2 by TGF-β1 was Smad3 dependent; whereas MMP-2 was Smad2 dependent. Smad2 and Smad3 both participated in MMP-9 expression. TGF-β1 reprogrammed mesenchymal fibroblast like cells robustly expressed collagen I and III and these was inhibited by SB-431542, a TGF-β receptor inhibitor. Our results indicate that EMT of porcine bladder UC cells is TGF-β1 dependent and is mediated through Smad2 and Smad3. TGF-β1 may be an important factor in the development of bladder fibrosis via an EMT mechanism. This identifies a potential amenable therapeutic target.
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تواريخ الأحداث: Date Created: 20131217 Date Completed: 20140402 Latest Revision: 20220711
رمز التحديث: 20240829
مُعرف محوري في PubMed: PMC3972392
DOI: 10.1007/s12079-013-0216-4
PMID: 24338442
قاعدة البيانات: MEDLINE
الوصف
تدمد:1873-9601
DOI:10.1007/s12079-013-0216-4