Fuzheng Huayu recipe, a traditional Chinese compound herbal medicine, attenuates renal interstitial fibrosis via targeting the miR-21/PTEN/AKT axis.

Abstract

OBJECTIVE:

MicroRNAs (miRNAs) may be viable targets for treating renal interstitial fibrosis (RIF). Fuzheng Huayu recipe (FZHY), a traditional Chinese compound herbal medicine, is often used in China to treat fibrosis. This study sought to assess the mechanisms through which FZHY influences miRNAs to treat RIF.

METHODS:

RIF was induced in rats by mercury chloride and treated with FZHY. Hydroxyproline content, Masson's staining and type I collagen expression were used to evaluate renal collagen deposition. Renal miRNA profiles were evaluated using a miRNA microarray. Those miRNAs that were differentially expressed following FZHY treatment were identified and subjected to bioinformatic analyses. The miR-21 target gene phosphatase and tensin homolog (PTEN) expression and AKT phosphorylation in kidney tissues were assessed via Western blotting. In addition, HK-2 human proximal tubule epithelial cells were treated using angiotensin II (Ang-II) to induce epithelial-to-mesenchymal transition (EMT), followed by FZHY exposure. miR-21 and PTEN expressions were evaluated via quantitative reverse transcription-polymerase chain reaction (qRT-PCR), while E-cadherin and α-smooth muscle actin (α-SMA) expressions were assessed by immunofluorescent staining and qRT-PCR. Western blotting was used to assess PTEN and AKT phosphorylation.

RESULTS:

FZHY significantly decreased kidney collagen deposition, hydroxyproline content and type I collagen level. The miRNA microarray identified 20 miRNAs that were differentially expressed in response to FZHY treatment. Subsequent bioinformatic analyses found that miR-21 was the key fibrosis-related miRNA regulated by FZHY. FZHY also decreased PTEN expression and AKT phosphorylation in fibrotic kidneys. Results from in vitro tests also suggested that FZHY promoted E-cadherin upregulation and inhibited α-SMA expression in Ang-II-treated HK-2 cells, effectively reversing Ang-II-mediated EMT. We also determined that FZHY reduced miR-21 expression, increased PTEN expression and decreased AKT phosphorylation in these cells.

CONCLUSION:

miR-21 is the key fibrosis-related miRNA regulated by FZHY. The ability of FZHY to modulate miR-21/PTEN/AKT signaling may be a viable approach for treating RIF.

• Authors: Qing-Lan Wang, Yan-Yan Tao, Hong-Dong Xie, Cheng-Hai Liu, Ping Liu
• Journal: Journal of integrative medicine (J Integr Med) Vol. 18 Issue 6 Pg. 505-513 (Nov 2020) ISSN: 2095-4964 [Print] Netherlands
• PMID: 32912827 (Publication Type: Journal Article)
• Copyright: Copyright © 2020 Shanghai Changhai Hospital. Published by Elsevier B.V. All rights reserved.

Chemical References

• Drugs, Chinese Herbal
• MicroRNAs
• fuzheng huayu
• mirn21 microRNA, rat
• Proto-Oncogene Proteins c-akt
• PTEN Phosphohydrolase
• Pten protein, rat

Topics

• Animals
• China
• Drugs, Chinese Herbal (pharmacology)
• Fibrosis
• Kidney (drug effects, pathology)
• MicroRNAs
• Nephritis, Interstitial (drug therapy)
• PTEN Phosphohydrolase
• Proto-Oncogene Proteins c-akt
• Rats