Salvianolic acid B attenuates tubulointerstitial fibrosis by inhibiting EZH2 to regulate the PTEN/Akt pathway
CONTEXT: Salvianolic acid B (SAB) can alleviate renal fibrosis and improve the renal function.
OBJECTIVE: To investigate the effect of SAB on renal tubulointerstitial fibrosis and explore its underlying mechanisms.
MATERIALS AND METHODS: Male C57 mice were subjected to unilateral ureteric obstruction (UUO) and aristolochic acid nephropathy (AAN) for renal fibrosis indication. Vehicle or SAB (10 mg/kg/d, i.p.) were given consecutively for 2 weeks in UUO mice while 4 weeks in AAN mice. The serum creatinine (Scr) and blood urine nitrogen (BUN) were measured. Masson's trichrome staining and the fibrotic markers (FN and α-SMA) were used to evaluate renal fibrosis. NRK-49F cells exposed to 2.5 ng/mL TGF-β were treated with SAB in the presence or absence of 20 μM 3-DZNep, an inhibitor of EZH2. The protein expression of EZH2, H3k27me3 and PTEN/Akt signaling pathway in renal tissue and NRK-49F cells were measured by Western blots.
RESULTS: SAB significantly improved the levels of Scr by 24.3% and BUN by 35.7% in AAN mice. SAB reduced renal interstitial collagen deposition by 34.7% in UUO mice and 72.8% in AAN mice. Both in vivo and in vitro studies demonstrated that SAB suppressed the expression of FN and α-SMA, increased PTEN and decreased the phosphorylation of Akt, which were correlated with the down-regulation of EZH2 and H3k27me3. The inhibition of EZH2 attenuated the anti-fibrotic effects of SAB in NRK-49Fs.
CONCLUSION: SAB might have therapeutic potential on renal fibrosis of CKD through inhibiting EZH2, which encourages further clinical trials.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:61 |
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| Enthalten in: |
Pharmaceutical biology - 61(2023), 1 vom: 30. Dez., Seite 23-29 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Lin, Pinglan [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 27.12.2022 Date Revised 27.12.2022 published: Print Citation Status MEDLINE |
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| doi: |
10.1080/13880209.2022.2148169 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM350366470 |
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| 100 | 1 | |a Lin, Pinglan |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Salvianolic acid B attenuates tubulointerstitial fibrosis by inhibiting EZH2 to regulate the PTEN/Akt pathway |
| 264 | 1 | |c 2023 | |
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| 500 | |a Date Completed 27.12.2022 | ||
| 500 | |a Date Revised 27.12.2022 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a CONTEXT: Salvianolic acid B (SAB) can alleviate renal fibrosis and improve the renal function | ||
| 520 | |a OBJECTIVE: To investigate the effect of SAB on renal tubulointerstitial fibrosis and explore its underlying mechanisms | ||
| 520 | |a MATERIALS AND METHODS: Male C57 mice were subjected to unilateral ureteric obstruction (UUO) and aristolochic acid nephropathy (AAN) for renal fibrosis indication. Vehicle or SAB (10 mg/kg/d, i.p.) were given consecutively for 2 weeks in UUO mice while 4 weeks in AAN mice. The serum creatinine (Scr) and blood urine nitrogen (BUN) were measured. Masson's trichrome staining and the fibrotic markers (FN and α-SMA) were used to evaluate renal fibrosis. NRK-49F cells exposed to 2.5 ng/mL TGF-β were treated with SAB in the presence or absence of 20 μM 3-DZNep, an inhibitor of EZH2. The protein expression of EZH2, H3k27me3 and PTEN/Akt signaling pathway in renal tissue and NRK-49F cells were measured by Western blots | ||
| 520 | |a RESULTS: SAB significantly improved the levels of Scr by 24.3% and BUN by 35.7% in AAN mice. SAB reduced renal interstitial collagen deposition by 34.7% in UUO mice and 72.8% in AAN mice. Both in vivo and in vitro studies demonstrated that SAB suppressed the expression of FN and α-SMA, increased PTEN and decreased the phosphorylation of Akt, which were correlated with the down-regulation of EZH2 and H3k27me3. The inhibition of EZH2 attenuated the anti-fibrotic effects of SAB in NRK-49Fs | ||
| 520 | |a CONCLUSION: SAB might have therapeutic potential on renal fibrosis of CKD through inhibiting EZH2, which encourages further clinical trials | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Aristolochic acid nephropathy | |
| 650 | 4 | |a Renal fibrosis | |
| 650 | 4 | |a chronic kidney diseases | |
| 650 | 4 | |a transforming growth factor-β | |
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| 700 | 1 | |a Wu, Ming |e verfasserin |4 aut | |
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| 700 | 1 | |a Huang, Di |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Chen |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Xuejun |e verfasserin |4 aut | |
| 700 | 1 | |a Ye, Chaoyang |e verfasserin |4 aut | |
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