Salvianolic Acid C Inhibits the Epithelial-Mesenchymal Transition and Ameliorates Renal Tubulointerstitial Fibrosis
Background: Salvianolic acid C (SAC) is a natural compound derived from Salvia miltiorrhiza that can protect against renal diseases. The aims of this work were to explore the effect of SAC on kidney tubulointerstitial fibrosis and study the associated mechanism. Methods: Models for unilateral ureter...
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| Format: | Article |
| Language: | English |
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IMR Press
2023-06-01
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| Series: | Frontiers in Bioscience-Landmark |
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| Online Access: | https://www.imrpress.com/journal/FBL/28/6/10.31083/j.fbl2806121 |
| _version_ | 1797789169032888320 |
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| author | Ming Wu Junyan Lin Di Huang Chaoyang Ye Dongping Chen |
| author_facet | Ming Wu Junyan Lin Di Huang Chaoyang Ye Dongping Chen |
| author_sort | Ming Wu |
| collection | DOAJ |
| description | Background: Salvianolic acid C (SAC) is a natural compound derived from Salvia miltiorrhiza that can protect against renal diseases. The aims of this work were to explore the effect of SAC on kidney tubulointerstitial fibrosis and study the associated mechanism. Methods: Models for unilateral ureteral obstruction (UUO) and aristolochic acid I (AAI) were established in mice to study renal tubulointerstitial fibrosis. Rat kidney fibroblasts (NRK-49F) and human kidney epithelial cells (HK2) were used as cellular models to evaluate the effects of SAC on kidney fibrosis. Results: Treatment with SAC for two weeks reduced the level of renal tubulointerstitial fibrosis in UUO- and AAI-induced fibrotic kidneys, as demonstrated by Masson’s staining and Western blot. SAC inhibited extracellular matrix protein expression in NRK-49F cells and TGF-β-stimulated HK2 cells in dose-dependent fashion. Moreover, SAC inhibited the expression of epithelial-mesenchymal transition (EMT) factors in animal and cellular models of kidney fibrosis, as well as the EMT-related transcription factor snail. Furthermore, SAC inhibited the fibrosis-related signaling pathway Smad3 in the fibrotic kidneys of two mouse models and in renal cells. Conclusions: We conclude that SAC inhibits EMT and ameliorates tubulointerstitial fibrosis through involvement of the signaling pathway for transforming growth factor-β (TGF-β)/Smad. |
| first_indexed | 2024-03-13T01:46:52Z |
| format | Article |
| id | doaj.art-ba718b0c1446443894151089cfeb3f82 |
| institution | Directory Open Access Journal |
| issn | 2768-6701 |
| language | English |
| last_indexed | 2024-03-13T01:46:52Z |
| publishDate | 2023-06-01 |
| publisher | IMR Press |
| record_format | Article |
| series | Frontiers in Bioscience-Landmark |
| spelling | doaj.art-ba718b0c1446443894151089cfeb3f822023-07-03T07:33:49ZengIMR PressFrontiers in Bioscience-Landmark2768-67012023-06-0128612110.31083/j.fbl2806121S2768-6701(23)00787-6Salvianolic Acid C Inhibits the Epithelial-Mesenchymal Transition and Ameliorates Renal Tubulointerstitial FibrosisMing Wu0Junyan Lin1Di Huang2Chaoyang Ye3Dongping Chen4Department of Nephrology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, 201203 Shanghai, ChinaDepartment of Nephrology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, 201203 Shanghai, ChinaDepartment of Nephrology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, 201203 Shanghai, ChinaDepartment of Nephrology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, 201203 Shanghai, ChinaDepartment of Nephrology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, 201203 Shanghai, ChinaBackground: Salvianolic acid C (SAC) is a natural compound derived from Salvia miltiorrhiza that can protect against renal diseases. The aims of this work were to explore the effect of SAC on kidney tubulointerstitial fibrosis and study the associated mechanism. Methods: Models for unilateral ureteral obstruction (UUO) and aristolochic acid I (AAI) were established in mice to study renal tubulointerstitial fibrosis. Rat kidney fibroblasts (NRK-49F) and human kidney epithelial cells (HK2) were used as cellular models to evaluate the effects of SAC on kidney fibrosis. Results: Treatment with SAC for two weeks reduced the level of renal tubulointerstitial fibrosis in UUO- and AAI-induced fibrotic kidneys, as demonstrated by Masson’s staining and Western blot. SAC inhibited extracellular matrix protein expression in NRK-49F cells and TGF-β-stimulated HK2 cells in dose-dependent fashion. Moreover, SAC inhibited the expression of epithelial-mesenchymal transition (EMT) factors in animal and cellular models of kidney fibrosis, as well as the EMT-related transcription factor snail. Furthermore, SAC inhibited the fibrosis-related signaling pathway Smad3 in the fibrotic kidneys of two mouse models and in renal cells. Conclusions: We conclude that SAC inhibits EMT and ameliorates tubulointerstitial fibrosis through involvement of the signaling pathway for transforming growth factor-β (TGF-β)/Smad.https://www.imrpress.com/journal/FBL/28/6/10.31083/j.fbl2806121renal fibrosisemtsacckd |
| spellingShingle | Ming Wu Junyan Lin Di Huang Chaoyang Ye Dongping Chen Salvianolic Acid C Inhibits the Epithelial-Mesenchymal Transition and Ameliorates Renal Tubulointerstitial Fibrosis Frontiers in Bioscience-Landmark renal fibrosis emt sac ckd |
| title | Salvianolic Acid C Inhibits the Epithelial-Mesenchymal Transition and Ameliorates Renal Tubulointerstitial Fibrosis |
| title_full | Salvianolic Acid C Inhibits the Epithelial-Mesenchymal Transition and Ameliorates Renal Tubulointerstitial Fibrosis |
| title_fullStr | Salvianolic Acid C Inhibits the Epithelial-Mesenchymal Transition and Ameliorates Renal Tubulointerstitial Fibrosis |
| title_full_unstemmed | Salvianolic Acid C Inhibits the Epithelial-Mesenchymal Transition and Ameliorates Renal Tubulointerstitial Fibrosis |
| title_short | Salvianolic Acid C Inhibits the Epithelial-Mesenchymal Transition and Ameliorates Renal Tubulointerstitial Fibrosis |
| title_sort | salvianolic acid c inhibits the epithelial mesenchymal transition and ameliorates renal tubulointerstitial fibrosis |
| topic | renal fibrosis emt sac ckd |
| url | https://www.imrpress.com/journal/FBL/28/6/10.31083/j.fbl2806121 |
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