Human umbilical cord MSC‑derived hepatocyte growth factor enhances autophagy in AOPP‑treated HK‑2 cells

Li,Minhui; Jiang,Tingting; Zhang,Wenying; Xie,Wei; Guo,Tingting; Tang,Xun; Zhang,Jun

doi:10.3892/etm.2020.8998

Human umbilical cord MSC‑derived hepatocyte growth factor enhances autophagy in AOPP‑treated HK‑2 cells

Authors:
- Minhui Li
- Tingting Jiang
- Wenying Zhang
- Wei Xie
- Tingting Guo
- Xun Tang
- Jun Zhang
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Affiliations: Blood Purification Center, Nanhai Hospital of Southern Medical University, Foshan, Guangdong 528244, P.R. China, Department of Nephrology, The People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi 530021, P.R. China, Department of Nephrology, Zhujiang Hospital of Southern Medical University, Guangzhou, Guangdong 510282, P.R. China
Published online on: July 13, 2020 https://doi.org/10.3892/etm.2020.8998
Pages: 2765-2773
Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Mesenchymal stem cell (MSC) transplantation may serve as an important treatment modality in chronic kidney disease (CKD); however, the underlying mechanisms remain unclear. Advanced oxidation protein products (AOPP) have been demonstrated to induce renal tubular epithelial cell (RTEC) injury via autophagy inhibition. Therefore, the present study was performed to investigate the role of human umbilical cord‑derived MSCs (hUC‑MSCs) in RTEC autophagy. AOPP‑treated HK‑2 cells were co‑cultured with hUC‑MSCs or treated with recombinant humanized hepatocyte growth factor (HGF). Western blotting was used to detect the levels of autophagy‑and PI3K/AKT/mTOR signaling pathway‑related proteins, and immunofluorescence staining was used to detect the levels of autophagy‑related proteins. The HGF protein levels in HK‑2 cells and the hUC‑MSC co‑culture system were measured. The cells were subsequently treated with tivantinib, an HGF competitive inhibitor, and the levels of autophagy‑related proteins were detected. Microtubule‑associated protein 1 light chain 3B (LC3B) II/LC3B I (LC3II/LC3I) and beclin 1 protein levels were increased, while p62, PI3K, phosphorylated (p)‑AKT and the p‑mTOR protein levels were decreased in AOPP‑treated HK‑2 cells co‑cultured with hUC‑MSC, compared with the group treated with AOPP only. Furthermore, HGF expression was increased in AOPP‑treated HK‑2 cells co‑cultured with hUC‑MSC, compared with the group treated with AOPP alone. When HGF activity was inhibited using tivantinib, these effects on LC3II/LC3I, beclin 1, p62, PI3K, p‑AKT, and p‑mTOR expression were partially reversed. Furthermore, the effects of tivantinib were reversed by Ly294002. In conclusion, the present study revealed that hUC‑MSCs partially reversed AOPP‑mediated inhibition of autophagy in HK‑2 cells via secretion of HGF, indicating that hUC‑MSCs may serve as a potential therapy for preventing the progression of CKD.

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