Related Experiment Video
Updated: Mar 12, 2026
Mechanism of Kemeng Fang's Inhibition of Podocyte Apoptosis in Rats with Membranous Nephropathy through the PI3K/AKT Signaling Pathway
Published on: August 23, 2024
Activation of FXR protects against renal fibrosis via suppressing Smad3 expression
Kai Zhao1,2, Jialin He1, Yan Zhang1
1Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Third Military Medical University, Chongqing 400038, China.
Abstract:
Renal fibrosis is the common pathway of most chronic kidney disease progression to end-stage renal failure. The nuclear receptor FXR (farnesoid X receptor), a multiple functional transcription factor, plays an important role in protecting against fibrosis. The TGFβ-Smad signaling has a central role in kidney fibrosis. However, it remains unclear whether FXR plays direct anti-fibrotic effect in renal fibrosis via regulating TGFβ-Smad pathway. In this study, we found that the level of FXR was negatively correlated with that of Smad3 and fibronectin (a marker of fibrosis) in human fibrotic kidneys. Activation of FXR suppressed kidney fibrosis and downregulated Smad3 expression, which was markedly attenuated by FXR antagonist. Moreover, the FXR-mediated repression of fibrosis was significantly alleviated by ectopic expression of Smad3. Luciferase reporter assay revealed that FXR activation inhibited the transcriptional activity of Smad3 gene promoter. The in vivo experiments showed that FXR agonist protected against renal fibrosis and downregulated Smad3 expression in UUO mice. These results suggested that FXR may serve as an important negative regulator for manipulating Smad3 expression, and the FXR/Smad3 pathway may be a novel target for the treatment of renal fibrosis.
Insights
The nuclear receptor FXR (farnesoid X receptor) activation suppresses kidney fibrosis by downregulating Smad3. This FXR/Smad3 pathway presents a potential new target for treating renal fibrosis.
Area of Science:
- Nephrology
- Molecular Biology
- Cell Biology
Background:
- Renal fibrosis is a key factor in chronic kidney disease progression.
- The nuclear receptor FXR is recognized for its protective role against fibrosis.
- The TGFβ-Smad signaling pathway is critically involved in kidney fibrosis.
Purpose of the Study:
- To investigate the direct anti-fibrotic effects of FXR in renal fibrosis.
- To determine if FXR regulates the TGFβ-Smad pathway in kidney fibrosis.
- To explore the therapeutic potential of the FXR/Smad3 pathway.
Main Methods:
- Correlation analysis of FXR, Smad3, and fibronectin in human fibrotic kidneys.
- In vitro studies using FXR activators and antagonists.
- In vivo studies in unilateral ureteric obstruction (UUO) mouse model.
- Luciferase reporter assays to assess promoter activity.
Main Results:
- FXR levels negatively correlated with Smad3 and fibronectin in human fibrotic kidneys.
- FXR activation suppressed kidney fibrosis and Smad3 expression, an effect reversed by FXR antagonists.
- Ectopic Smad3 expression alleviated FXR-mediated fibrosis suppression.
- FXR activation inhibited the Smad3 gene promoter activity.
- FXR agonist treatment protected against renal fibrosis and reduced Smad3 expression in UUO mice.
Conclusions:
- FXR acts as a negative regulator of Smad3 expression in renal fibrosis.
- The FXR/Smad3 pathway is a potential novel therapeutic target for renal fibrosis treatment.
More Related Videos
10:21Mechanistic Insight into the Development of TNBS-Mediated Intestinal Fibrosis and Evaluating the Inhibitory Effects of Rapamycin
Published on: September 12, 2019
09:16Suppression of Pro-fibrotic Signaling Potentiates Factor-mediated Reprogramming of Mouse Embryonic Fibroblasts into Induced Cardiomyocytes
Published on: June 3, 2018
Related Concept Videos
01:16TGF - β Signaling Pathway
01:22PI3K/mTOR/AKT Signaling Pathway
02:26NF-κB-dependent Signaling Pathway
NF-κB-dependent Signaling Mechanism
The...