Diabetic nephropathy (DN) is a serious complication in type 1 and type 2 diabetes, and renal interstitial fibrosis plays a key role in DN progression. Here, we aimed to probe into the role and potential mechanism of miR-483-5p in DN-induced renal interstitial fibrosis. In this study, we corroborated that miR-483-5p expression was lessened in type 1 and type 2 diabetic mice kidney tissues and high glucose (HG)-stimulated tubular epithelial cells (TECs), and raised in the exosomes derived from renal tissues in type 1 and type 2 diabetic mice. miR-483-5p restrained the expressions of fibrosis-related genes in vitro and renal interstitial fibrosis in vivo. Mechanistically, miR-483-5p bound both TIMP2 and MAPK1, and TIMP2 and MAPK1 were bound up with the regulation of miR-483-5p on renal TECs under HG conditions. Importantly, HNRNPA1-mediated exosomal sorting transported cellular miR-483-5p out of TECs into the urine. Our results expounded that HNRNPA1-mediated exosomal sorting transported cellular miR-483-5p out of TECs into the urine, thus lessening the restraint of cellular miR-483-5p on MAPK1 and TIMP2 mRNAs, and ultimately boosting extracellular matrix deposition and the progression of DN-induced renal interstitial fibrosis.
From a spatial perspective, this paper constructs a spatial Durbin model based on the adjacent weight matrix to analyze the impact of environmental regulation on the development of renewable energy in 30 provinces (autonomous regions and municipalities directly under the Central Government) in China from 2007 to 2020. The results show that: 1) Both environmental regulation and renewable energy development have positive spatial autocorrelation, and form relatively similar spatial agglomeration areas, specifically showing the characteristics of "high-high" agglomeration in resource-rich areas, and "low-low" agglomeration in resource-scarce areas. 2) In general, the intensity of environmental regulation in this province has a significant role in promoting the development of renewable energy and has a significant spatial spillover effect on the development of renewable energy in neighboring provinces due to the influence of geographical distance, economic level, infrastructure construction and other factors. 3) The moderating effect results show that infrastructure construction and electricity demand play an inverse moderating role between environmental regulation and renewable energy development. 4) From the perspective of different regions, the impact of environmental regulation on the development of renewable energy is heterogeneous. Based on the research conclusions, this paper finally puts forward some policy suggestions, such as strengthening the environmental assessment and incentive system, strengthening the cooperation between local governments and rationally optimizing the energy structure.
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