Abstract
BACKGROUND: Oxidative stress damage is the important mechanism that promotes the process of fibrosis. Whether mesenchymal stem cells (MSCs) regulate mitochondrial dynamics and oxidative stress via armadillo repeat containing 1 (ARMC1) in renal fibrosis? METHODS: Using proteomics analysis, compare the significant differences in renal tissue proteins before and after MSCs intervention in adenine-induced nephropathy. Using a lentiviral vector to overexpress the ARMC1 gene in HK-2 cells, with the empty vector as a control. MSCs conditioned media (MSCs-CM) was applied to TGF-β1 treated cells, and MSCs were used in a cisplatin-induced nephropathy mouse model to assess mitochondrial dynamics, ROS generation, antioxidant stress, and fibrosis indicators, with Mdivi-1 (a Drp1 inhibitor) and Apocynin (a selective NADPH oxidase inhibitor) as positive controls. RESULTS: Renal proteomics showed that MSCs increased ARMC1 protein in the renal tissue of adenine nephropathy (3.521 times). In vitro, MSCs-CM increased ARMC1, reduced DRP1, and enhanced OPA1 and MFN2, lowering ROS, boosting mitochondrial bioactivity, and increasing antioxidant proteins NRF2, SOD1, SOD2, and CAT while decreasing fibrosis markers α-SMA, FN, COL-I, and KIM-1, and raising E-cadherin. The indicator variations in ARMC1-OE cells and OE-Con cells were similar between subgroups; Notably, under identical treatment conditions, the shifts in indicators within ARMC1-OE cells were more significant than those observed in OE-Con cells. In cisplatin-induced nephropathy mice, MSCs, Apocynin, and Mdivi-1 improved renal function and reduced interstitial collagen deposition, inhibited mitochondrial fission, enhanced antioxidant capacity, and reduced fibrosis. However, individual interventions were found to be less effective than their combined counterparts, with the synergistic impact of MSCs and Mdivi-1 achieving the most remarkable outcomes. CONCLUSION: MSCs have the potential to improve renal fibrosis by influencing mitochondrial dynamics and oxidative stress through the upregulation of ARMC1 expression. ARMC1 may be an effective target for anti-fibrosis.