Ureteral Obstruction-Induced Renal Fibrosis: An In Vivo Platform for Mechanistic Discovery and Therapeutic Intervention*Corresponding Author: Dr. Paul J. Higgins, Center for Cell Biology & Cancer Research, Albany Medical College, 47 New Scotland Avenue, Albany, New York 12208, USA, Tel: 518-262-5168, Email: [email protected]
Received Date: Jun 30, 2012 / Accepted Date: Jul 02, 2012 / Published Date: Jul 03, 2012
Citation: Dobberfuhl AD, Samarakoon R, Higgins CE, Mian BM, Overstreet JM, et al. (2012) Ureteral Obstruction-Induced Renal Fibrosis: An In Vivo Platform for Mechanistic Discovery and Therapeutic Intervention. Cell Dev Biol 1:e107.DOI: 10.4172/2168-9296.1000e107
Copyright: © 2012 . This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Interstitial fibrosis, resulting in renal tissue destruction and progressive impairment of organ function, is a hallmark of end-stage kidney disease . The primary sources of matrix synthesis during renal fibrogenesis are activated fibroblasts or myofibroblasts. While their origin remains uncertain, this cell type-predictor of disease progression likely derives largely from resident fibroblasts and epithelial-to-mesenchymal transdifferentiated (EMT) tubular epithelial cells . The transforming growth factor-β (TGF-β)/SMAD system is a potent, perhaps the most well-characterized, inducer of myofibroblast differentiation and EMT. TGF-β drives EMT in renal epithelial cells and promotes fibrosis in animal models by engaging effector pathways and their downstream target genes that impact both the inflammatory and scarring stages of the injury response . SMAD-mediated signaling initiated by TGF-β is pivotal for induction of EMT, fibroblast activation and renal fibrosis [2,3]. SMAD3, in particular, appears critical in several in vivo models of renal fibrosis. This was, indeed, confirmed by the finding that SMAD3-deficient mice are significantly protected from disease progression. TGF-β also activates non-SMAD-dependent pathways  that impact the expression of pro-fibrotic genes. The continued characterization of such highly-interactive transduction events initiated by TGF-β/TGF-β receptor interactions will likely lead to identification of novel opportunities for anti-fibrotic therapy.