Published online Aug 15, 2023. doi: 10.4239/wjd.v14.i8.1234
Peer-review started: April 20, 2023
First decision: June 1, 2023
Revised: June 12, 2023
Accepted: July 7, 2023
Article in press: July 7, 2023
Published online: August 15, 2023
Processing time: 113 Days and 3.5 Hours
Dysregulated microRNA (miRNA) is crucial in the progression of diabetic nephropathy (DN).
To investigate the potential molecular mechanism of Icariin (ICA) in regulating endoplasmic reticulum (ER) stress-mediated apoptosis in high glucose (HG)-induced primary rat kidney cells (PRKs), with emphasis on the role of miR-503 and sirtuin 4 (SIRT4) in this process.
Single intraperitoneal injection of streptozotocin (65 mg/kg) in Sprague-Dawley rats induce DN in the in vivo hyperglycemic model. Glucose-treated PRKs were used as an in vitro HG model. An immunofluorescence assay identified isolated PRKs. Cell Counting Kit-8 and flow cytometry analyzed the effect of ICA treatment on cell viability and apoptosis, respectively. Real-time quantitative polymerase chain reaction and western blot analyzed the levels of ER stress-related proteins. Dual luciferase analysis of miR-503 binding to downstream SIRT4 was performed.
ICA treatment alleviated the upregulated miR-503 expression in vivo (DN) and in vitro (HG). Mechanistically, ICA reduced HG-induced miR-503 overexpression, thereby counteracting its function in downregulating SIRT4 levels. ICA regulated the miR-503/SIRT4 axis and subsequent ER stress to alleviate HG-induced PRKs injury.
ICA reduced HG-mediated inhibition of cell viability, promotion of apoptosis, and ER stress in PRKs. These effects involved regulation of the miR-503/SIRT4 axis. These findings indicate the potential of ICA to treat DN, and implicate miR-503 as a viable target for therapeutic interventions in DN.
Core Tip: Icariin (ICA) has shown promise as a potential therapeutic agent for diabetes mellitus (DM) by regulating the miR-503-5p/sirtuin 4 (SIRT4) axis and subsequent endoplasmic reticulum (ER) stress. This study found that ICA treatment reduced high glucose-induced inhibition of cell viability, promotion of apoptosis, and ER stress in primary rat kidney cells. Mechanistically, ICA inhibited the upregulation of miR-503-5p and subsequently restored SIRT4 levels, thereby alleviating high glucose-induced injury in cells. These findings implicate ICA as a candidate drug for the treatment of DM and miR-503-5p as a potential therapeutic target for this disease.