Related Experiment Video
Updated: May 30, 2026
Molecular Analysis of Endothelial-mesenchymal Transition Induced by Transforming Growth Factor-β Signaling
Published on: August 3, 2018
TGF-β/Smad3 signaling promotes renal fibrosis by inhibiting miR-29
Wei Qin1, Arthur C K Chung, Xiao R Huang
1Department of Medicine and Therapeutics, and Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, NT, Hong Kong, China.
Abstract:
TGF-β/Smad3 signaling promotes fibrosis, but the development of therapeutic interventions involving this pathway will require the identification and ultimate targeting of downstream fibrosis-specific genes. In this study, using a microRNA microarray and real-time PCR, wild-type mice had reduced expression of miR-29 along with the development of progressive renal fibrosis in obstructive nephropathy. In contrast, Smad3 knockout mice had increased expression of miR-29 along with the absence of renal fibrosis in the same model of obstruction. In cultured fibroblasts and tubular epithelial cells, Smad3 mediated TGF-β(1)-induced downregulation of miR-29 by binding to the promoter of miR-29. Furthermore, miR-29 acted as a downstream inhibitor and therapeutic microRNA for TGF-β/Smad3-mediated fibrosis. In vitro, overexpression of miR-29b inhibited, but knockdown of miR-29 enhanced, TGF-β(1)-induced expression of collagens I and III by renal tubular cells. Ultrasound-mediated gene delivery of miR-29b either before or after established obstructive nephropathy blocked progressive renal fibrosis. In conclusion, miR-29 is a downstream inhibitor of TGF-β/Smad3-mediated fibrosis and may have therapeutic potential for diseases involving fibrosis.
Insights
MicroRNA-29 (miR-29) inhibits kidney fibrosis by downregulating the TGF-β/Smad3 pathway. Restoring miR-29 levels offers a potential therapeutic strategy for fibrotic kidney diseases.
Area of Science:
- Molecular Biology
- Renal Physiology
- MicroRNA Therapeutics
Background:
- Transforming growth factor-beta (TGF-β)/Smad3 signaling is a key driver of fibrosis.
- Targeting downstream fibrosis-specific genes is crucial for developing effective therapies.
- MicroRNAs (miRNAs) play significant roles in regulating cellular processes, including fibrosis.
Purpose of the Study:
- To investigate the role of miR-29 in TGF-β/Smad3-mediated renal fibrosis.
- To determine if miR-29 acts as a therapeutic agent for fibrotic kidney disease.
Main Methods:
- Utilized a mouse model of obstructive nephropathy.
- Employed microRNA microarray and real-time PCR to assess miR-29 expression.
- Performed in vitro studies using cultured fibroblasts and renal tubular epithelial cells.
- Investigated the effect of miR-29b gene delivery via ultrasound mediation.
Main Results:
- Wild-type mice with obstructive nephropathy showed reduced miR-29 expression and developed renal fibrosis.
- Smad3 knockout mice exhibited increased miR-29 expression and lacked renal fibrosis.
- Smad3 mediated TGF-β(1)-induced downregulation of miR-29.
- Overexpression of miR-29b inhibited, while knockdown enhanced, TGF-β(1)-induced collagen expression.
- miR-29b gene delivery successfully blocked progressive renal fibrosis in vivo.
Conclusions:
- miR-29 functions as a downstream inhibitor of TGF-β/Smad3-mediated fibrosis.
- miR-29 demonstrates therapeutic potential for treating fibrotic diseases, particularly in the kidney.
