1. Academic Validation
  2. Capsaicin ameliorates renal fibrosis by inhibiting TGF-β1-Smad2/3 signaling

Capsaicin ameliorates renal fibrosis by inhibiting TGF-β1-Smad2/3 signaling

  • Phytomedicine. 2022 Jun;100:154067. doi: 10.1016/j.phymed.2022.154067.
Zhenyu Liu 1 Weili Wang 2 Xueqin Li 1 Sha Tang 1 Dongwei Meng 3 Wenli Xia 1 Hong Wang 1 Yuzhang Wu 3 Xinyuan Zhou 4 Jingbo Zhang 5
Affiliations

Affiliations

  • 1 Department of Nephrology, the Key Laboratory for the Prevention and Treatment of Chronic Kidney Disease of Chongqing, Chongqing Clinical Research Center of Kidney and Urology Diseases, Xinqiao Hospital, Army Medical University (Third Military Medical University), Chongqing 400037, PR China.
  • 2 School of Medicine, Chongqing University, Chongqing 400030, PR China; College of Bioengineering, Chongqing University, Chongqing 400044, PR China.
  • 3 Institute of Immunology, College of Basic Medical Sciences, Third Military Medical University, Chongqing 400038, PR China.
  • 4 Institute of Immunology, College of Basic Medical Sciences, Third Military Medical University, Chongqing 400038, PR China. Electronic address: [email protected]
  • 5 Department of Nephrology, the Key Laboratory for the Prevention and Treatment of Chronic Kidney Disease of Chongqing, Chongqing Clinical Research Center of Kidney and Urology Diseases, Xinqiao Hospital, Army Medical University (Third Military Medical University), Chongqing 400037, PR China. Electronic address: [email protected]
Abstract

Background and purpose: Chronic kidney disease (CKD), characterized by renal fibrosis, is a global refractory disease with few effective therapeutic strategies. It has been reported that capsaicin exerts many pharmacological effects including liver and cardiac fibrosis. However, whether capsaicin plays a therapeutic role in renal fibrosis remains unclear.

Methods: We investigated antifibrotic effects of capsaicin in two mouse renal fibrosis models as follows: C57BL/6J mice were subjected to unilateral ureteral obstruction (UUO) and fed with an adenine-rich diet. We uncovered and verified the mechanisms of capsaicin in human proximal tubular epithelial cells (HK2). We mainly used histochemistry, immunohistochemistry and immunofluorescence staining, western blot assay, biochemical examination and other tools to examine the effects of capsaicin on renal fibrosis and the underlying mechanisms.

Results: Capsaicin treatment significantly alleviated fibronectin and collagen depositions in the tubulointerstitium of the injured kidneys from UUO and adenine-fed mice. Meanwhile, capsaicin treatment obviously reduced α-SMA expression. Moreover, capsaicin treatment dramatically protected against the phenotypic alteration of tubular epithelial cells by increasing E-cadherin expression and decreasing vimentin expression during renal fibrosis. Mechanistically, capsaicin treatment effectively suppressed α-SMA and vimentin expressions but promoted E-cadherin expression in HK2 cells mainly through the inhibition of TGF-β1-Smad2/3 signaling.

Conclusion: Capsaicin significantly ameliorated renal fibrosis possibly by retarding the activation of myofibroblasts and protecting against the phenotypic alteration of tubular epithelial cells mainly through the inhibition of TGF-β1-Smad2/3 signaling. Thus, our findings may provide a new insight into the clinical application of capsaicin in renal fibrosis.

Keywords

Capsaicin; Renal fibrosis; TGF-β1; TRPV1; Tubular epithelial cell.

Figures
Products