Related Experiment Video
Updated: Jun 12, 2026
Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
Published on: October 27, 2020
miR-192 mediates TGF-beta/Smad3-driven renal fibrosis
Arthur C K Chung1, Xiao R Huang, Xiaoming Meng
1Department of Medicine and Therapeutics and Li Ka Shing Institute of Health Sciences, Chinese University of Hong Kong, Hong Kong, China.
Abstract:
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-beta1-induced miR-192 expression. Furthermore, Smad3 but not Smad2 mediated TGF-beta1-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-beta1-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.
Insights
MicroRNA-192 (miR-192) is upregulated in fibrotic kidneys and mediates renal fibrosis through the TGF-beta/Smad3 pathway. Inhibiting miR-192 can block fibrosis development, highlighting its role in kidney disease.
Area of Science:
- Nephrology
- Molecular Biology
- Biochemistry
Background:
- Transforming growth factor-beta (TGF-beta)/Smad3 signaling is a key driver of renal fibrosis.
- The precise mechanisms regulating profibrotic genes in kidney fibrosis remain incompletely understood.
Purpose of the Study:
- To investigate the role of microRNA-192 (miR-192) in mediating renal fibrosis via a Smad3-dependent pathway.
- To elucidate the regulatory relationship between TGF-beta/Smad signaling and miR-192 expression in kidney fibrosis.
Main Methods:
- Microarray and real-time PCR to assess miR-192 expression in fibrotic kidneys.
- Utilizing Smad7 manipulation (deletion and overexpression) in obstructive kidney disease models and in vitro cell cultures.
- Investigating Smad3 and Smad2 binding to the miR-192 promoter.
- Employing miR-192 mimics and inhibitors to assess functional impact on collagen expression.
Main Results:
- miR-192 expression was tightly associated with TGF-beta/Smad signaling activation in fibrotic kidneys.
- Smad7 deletion enhanced miR-192 expression and fibrosis, while Smad7 overexpression inhibited both.
- Smad3, not Smad2, mediated TGF-beta1-induced miR-192 expression by binding to its promoter.
- miR-192 mimic promoted and inhibitor blocked TGF-beta1-induced collagen matrix expression.
Conclusions:
- miR-192 is a critical downstream mediator of TGF-beta/Smad3 signaling in the pathogenesis of renal fibrosis.
- Targeting miR-192 presents a potential therapeutic strategy for kidney fibrosis.
