Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Blood Glucose / metabolism
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Cell Line
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Diabetes Mellitus, Experimental / blood
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Diabetes Mellitus, Experimental / complications
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Diabetes Mellitus, Type 1 / blood
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Diabetes Mellitus, Type 1 / complications
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Diabetes Mellitus, Type 2 / blood
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Diabetes Mellitus, Type 2 / complications
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Diabetic Nephropathies / etiology
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Diabetic Nephropathies / genetics
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Diabetic Nephropathies / metabolism*
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Diabetic Nephropathies / pathology
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Disease Progression
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Epithelial Cells / metabolism*
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Epithelial Cells / pathology
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Exosomes / genetics
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Exosomes / metabolism*
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Fibrosis
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Gene Expression Regulation
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Heterogeneous Nuclear Ribonucleoprotein A1 / genetics
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Heterogeneous Nuclear Ribonucleoprotein A1 / metabolism*
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Heterogeneous Nuclear Ribonucleoprotein A1 / urine
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Humans
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Kidney Tubules / metabolism*
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Kidney Tubules / pathology
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Male
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Mice
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Mice, Inbred C57BL
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MicroRNAs / genetics
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MicroRNAs / metabolism*
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Mitogen-Activated Protein Kinase 1 / genetics
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Mitogen-Activated Protein Kinase 1 / metabolism
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Protein Transport
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Tissue Inhibitor of Metalloproteinase-2 / genetics
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Tissue Inhibitor of Metalloproteinase-2 / metabolism
Substances
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Blood Glucose
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Heterogeneous Nuclear Ribonucleoprotein A1
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Hnrnpa1 protein, mouse
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MicroRNAs
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Mirn483 microRNA, mouse
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Timp2 protein, mouse
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Tissue Inhibitor of Metalloproteinase-2
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Mapk1 protein, mouse
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Mitogen-Activated Protein Kinase 1