Journal
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
Volume 21, Issue 8, Pages 1317-1325Publisher
AMER SOC NEPHROLOGY
DOI: 10.1681/ASN.2010020134
Keywords
-
Categories
Funding
- Research Grant Council of the Hong Kong SAR, China [GRF 768207, 767508, CUHK5/CRF/09, 763908, 764109]
Ask authors/readers for more resources
TGF-beta/Smad3 promotes renal fibrosis, but the mechanisms that regulate profibrotic genes remain unclear. We hypothesized that miR-192, a microRNA expressed in the kidney may mediate renal fibrosis in a Smad3-dependent manner. Microarray and real-time PCR demonstrated a tight association between upregulation of miR-192 in the fibrotic kidney and activation of TGF-beta/Smad signaling. Deletion of Smad7 promoted miR-192 expression and enhanced Smad signaling and fibrosis in obstructive kidney disease. In contrast, overexpression of Smad7 to block TGF-beta/Smad signaling inhibited miR-192 expression and renal fibrosis in the rat 5/6 nephrectomy model; in vitro, overexpression of Smad7 in tubular epithelial cells abolished TGF-beta 1-induced miR-192 expression. Furthermore, Smad3 but not Smad2 mediated TGF-beta 1-induced miR-192 expression by binding to the miR-192 promoter Last, overexpression of a miR-192 mimic promoted and addition of a miR-192 inhibitor blocked TGF-beta 1-induced collagen matrix expression. Taken together, miR-192 may be a critical downstream mediator of TGF-beta/Smad3 signaling in the development of renal fibrosis.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available