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

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.

Anti-Hyperglycemic Effect of Magnesium-Enhanced Alkaline-Reduced Water on High Glucose-Induced Oxidative Stress in Renal Tubular Epithelial Cells

“…The physiochemical characteristics of ARW enable it to easily penetrate the cell membrane, resulting in increased metabolism due to its antioxidative properties [42]. Furthermore, endogenous HGF expression in renal tubular cells has been reported in a few studies [11]. Correspondingly, this study strengthens the physiological role of HGF in PTEC, which warrants deeper investigation.…”

“…Accumulating evidence has shown that MMPs are the main factors of extracellular matrix (ECM) degradation and that they activate multiple growth factors and cytokines linked with hypertrophy of kidneys, proliferation of tubular cells and fibrosis [9,10]. In addition, studies have shown that hepatocyte growth factor (HGF) and α-smooth muscle actin (α-SMA) play a central role in ECM accumulation in diabetic kidneys [11,12]. Therefore, protecting kidney cells by suppressing OS in DM may be a possible therapeutic approach for DN treatment.…”

Mesenchymal Stem Cell Therapy in Kidney Diseases: Potential and Challenges

“…Feng et al 140 found that transplantation of sirtuin3-overexpression amniotic fluid stem cells serves as promoting therapeutic strategies for DN through activation of mitophagy and inhibition of apoptosis. Other studies confirmed that UCMSCs enhanced autophagy in advanced oxidation protein products–treated HK-2 cells through inactivation of the PI3K/Akt/mTOR pathway 141 , 142 . Intriguingly, upregulation of autophagy remarkably increased the secretion of TGF-β1 from MSCs and suppressed the proliferation of CD4 + T lymphocytes 143 , whereas inhibition of autophagy reduced the responsiveness of T cells to mitogen IL-2 and increased the production of immunosuppressive prostaglandin E2 144 .…”

Bone marrow mesenchymal stem cells stimulated by tumor necrosis factor-α can promote the repair of fatty liver cell oxidative stress injury and fatty liver ischemia-reperfusion injury

“…Yu-Ting He 20 and others used hepatocytes/MSCs at a culture ratio of 5:1 for culture to generate stable primary hepatocytes. MINHUI LI 21 and others co-cultured hUc-MSC and HK-2 cells at a ratio of 12:1 to prove that hepatocyte growth factor derived from human umbilical cord blood mesenchymal stem cells promoted autophagy in HK-2 cells treated with AOPP. Studies have considered that the co-culture system can make BMSCs differentiate into hepatocytes to a certain extent 2125 , but the co-culture experiment of BMSCs such as Lange has proved that the proportion of BMSCs differentiation into hepatocytes is very small in a relatively short period of time 26 , the impact on the experiment is not large.…”