Salvianolic acid B attenuates renal interstitial fibrosis by regulating the HPSE/SDC1 axis

Mol Med Rep. 2020 Aug;22(2):1325-1334. doi: 10.3892/mmr.2020.11229. Epub 2020 Jun 15.

Abstract

Salvianolic acid B (Sal B) is one of the main water‑soluble components of Salvia miltiorrhiza Bge. Numerous reports have demonstrated that it could exert significant renal‑protective effects, but the underlying mechanism remains unclear. The present study demonstrated that Sal B could alleviate renal injury by regulating the heparanase/syndecan‑1 (HPSE/SDC1) axis. In vivo, the serum creatinine, blood urea nitrogen, transforming growth factor‑β1 (TGF‑β1) and fibroblast growth factor‑2 (FGF‑2) levels, and the histopathological changes of mice kidneys were examined. Sal B could notably reduce the renal injury caused by left ureteral ligation. In vitro, Sal B downregulated the expression levels of HPSE/FGF‑2/TGF‑β1/α‑smooth muscle actin and upregulated the expression levels of SDC1/E‑cadherin in angiotensin II‑stimulated HK‑2 cells in a dose‑dependent manner. In summary, to the best of the authors' knowledge, the present study provided evidence for the first time that Sal B could exert renal‑protective effects via the inhibition of the HPSE/SDC1 axis, and these results suggest that the administration of Sal B may be a novel therapeutic strategy in treating renal interstitial fibrosis.

Keywords: salvianolic acid B; renal interstitial fibrosis; heparanase; syndecan-1; angiotensin ii.

MeSH terms

  • Animals
  • Benzofurans / therapeutic use*
  • Cell Line
  • Fibrosis / drug therapy*
  • Glucuronidase / metabolism*
  • Humans
  • Kidney / drug effects*
  • Kidney / pathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Protective Agents / therapeutic use
  • Renal Insufficiency, Chronic / drug therapy*
  • Syndecan-1 / metabolism*

Substances

  • Benzofurans
  • Protective Agents
  • SDC1 protein, human
  • Syndecan-1
  • salvianolic acid B
  • heparanase
  • Glucuronidase