Abstract
Diabetic nephropathy (DN) is the most serious long-term microvascular complication of diabetes, which mainly causes podocyte injury. Many studies have shown that microRNAs play a vital role in the development of DN. Studies have shown that miR-203-3p is involved in mesangial cell proliferation and apoptosis of DN mice. Therefore, we speculated that miR-203-3p might be related to the development of DN, but our study does not provide any evidence. In animal experiments, diabetic mice (db/db) were transfected with iR-203-3p overexpression lentiviral vectors (LV-miR-203-3p) and their control (LV-miR-con), with normal mice (db/m) being used as the control. High glucose (HG)-induced podocytes were used to construct a DN cell model in vitro. The expression levels of miR-203-3p, Semaphorin 3A (Sema3A) and inflammatory cytokines were detected by quantitative real-time polymerase chain reaction. Also, serum creatinine and blood urea nitrogen levels were used to evaluate the degree of renal injury in DN mice. Sema3A and apoptosis-related protein levels were assessed by the western blot analysis. Enzyme-linked immunosorbent assay was used to determine the different oxidative stress-related indicators and inflammatory cytokines. Flow cytometry and caspase-3 activity detection were used to analyze the degree of podocyte apoptosis. Our results suggested that the expression of miR-203-3p was lower in DN mice and in HG-induced podocytes. Overexpression of miR-203-3p reduced the body weight, blood glucose and renal injury of DN mice in vivo, as well as relieve the oxidative stress, inflammatory response and apoptosis of HG-induced podocytes in vitro. Functionally, Sema3A was a target of miR-203-3p, and Sema3A overexpression reversed the inhibitory effect of miR-203-3p on HG-induced podocyte injury. Our findings revealed that miR-203-3p alleviated the podocyte injury induced by HG via regulating Sema3A expression, suggesting that miR-203-3p might be a new therapeutic target to improve the progression of DN.
Highlights
Diabetic nephropathy (DN) is one of the most severe and harmful chronic complications of diabetes, which can cause end-stage renal disease [1,2]
This study aimed to explore the effect and mechanism of miR-203-3p on the oxidative stress, inflammatory response and apoptosis of podocytes induced by High glucose (HG) to provide potential therapeutic targets for DN
We investigated the expression of miR203-3p in HG-induced podocytes. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to detect the expression of miR-203-3p in different concentrations of glucose (0, 10, 20, 30 and 40 mM) and different times (0, 12, 24 and 48 h) after HG treatment
Summary
Diabetic nephropathy (DN) is one of the most severe and harmful chronic complications of diabetes, which can cause end-stage renal disease [1,2]. Renal disease is the leading cause of death and disability in diabetic patients [3]. DN has become a major global public health problem, which seriously affects people’s living standards. The study of the molecular mechanisms of DN can provide a more targeted approach for the treatment of DN. Metabolic damage caused by hyperglycemia is the key to the development of DN [4,5]. High glucose (HG) can cause podocyte injury, which is an essential factor for DN progression [6]. DN is accompanied by renal oxidative stress and inflammatory response [7,8]. Studies have shown that HG can induce the apoptosis, oxidative stress and inflammatory response of podocytes [9–11].
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
