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Capsaicin ameliorates renal fibrosis by inhibiting TGF-β1-Smad2/3 signaling.
- Source :
-
Phytomedicine : international journal of phytotherapy and phytopharmacology [Phytomedicine] 2022 Jun; Vol. 100, pp. 154067. Date of Electronic Publication: 2022 Mar 21. - Publication Year :
- 2022
-
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.<br />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.<br />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.<br />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.<br /> (Copyright © 2022 Elsevier GmbH. All rights reserved.)
- Subjects :
- Adenine
Animals
Cadherins metabolism
Disease Models, Animal
Fibrosis
Kidney
Mice
Mice, Inbred C57BL
Smad2 Protein metabolism
Smad3 Protein
Vimentin metabolism
Capsaicin pharmacology
Kidney Diseases drug therapy
Renal Insufficiency, Chronic drug therapy
Transforming Growth Factor beta1 metabolism
Ureteral Obstruction pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1618-095X
- Volume :
- 100
- Database :
- MEDLINE
- Journal :
- Phytomedicine : international journal of phytotherapy and phytopharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 35349832
- Full Text :
- https://doi.org/10.1016/j.phymed.2022.154067