HNRNPA1-mediated exosomal sorting of miR-483-5p out of renal tubular epithelial cells promotes the progression of diabetic nephropathy-induced renal interstitial fibrosis
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 cor...
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2021-03-01
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| Series: | Cell Death and Disease |
| Online Access: | https://doi.org/10.1038/s41419-021-03460-x |
| _version_ | 1818368717718814720 |
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| author | DongWei Liu FengXun Liu ZhengYong Li ShaoKang Pan JunWei Xie ZiHao Zhao ZhenJie Liu JiaHui Zhang ZhangSuo Liu |
| author_facet | DongWei Liu FengXun Liu ZhengYong Li ShaoKang Pan JunWei Xie ZiHao Zhao ZhenJie Liu JiaHui Zhang ZhangSuo Liu |
| author_sort | DongWei Liu |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-13T23:12:23Z |
| format | Article |
| id | doaj.art-9a0e715d49de40a384be02da3c4ac7e0 |
| institution | Directory Open Access Journal |
| issn | 2041-4889 |
| language | English |
| last_indexed | 2024-12-13T23:12:23Z |
| publishDate | 2021-03-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death and Disease |
| spelling | doaj.art-9a0e715d49de40a384be02da3c4ac7e02022-12-21T23:28:04ZengNature Publishing GroupCell Death and Disease2041-48892021-03-0112311510.1038/s41419-021-03460-xHNRNPA1-mediated exosomal sorting of miR-483-5p out of renal tubular epithelial cells promotes the progression of diabetic nephropathy-induced renal interstitial fibrosisDongWei Liu0FengXun Liu1ZhengYong Li2ShaoKang Pan3JunWei Xie4ZiHao Zhao5ZhenJie Liu6JiaHui Zhang7ZhangSuo Liu8Department of Nephrology, the First Affiliated Hospital of Zhengzhou UniversityDepartment of Nephrology, the First Affiliated Hospital of Zhengzhou UniversityDepartment of Nephrology, the First Affiliated Hospital of Zhengzhou UniversityDepartment of Nephrology, the First Affiliated Hospital of Zhengzhou UniversityDepartment of Nephrology, the First Affiliated Hospital of Zhengzhou UniversityDepartment of Nephrology, the First Affiliated Hospital of Zhengzhou UniversityDepartment of Nephrology, the First Affiliated Hospital of Zhengzhou UniversityDepartment of Nephrology, the First Affiliated Hospital of Zhengzhou UniversityDepartment of Nephrology, the First Affiliated Hospital of Zhengzhou UniversityAbstract 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.https://doi.org/10.1038/s41419-021-03460-x |
| spellingShingle | DongWei Liu FengXun Liu ZhengYong Li ShaoKang Pan JunWei Xie ZiHao Zhao ZhenJie Liu JiaHui Zhang ZhangSuo Liu HNRNPA1-mediated exosomal sorting of miR-483-5p out of renal tubular epithelial cells promotes the progression of diabetic nephropathy-induced renal interstitial fibrosis Cell Death and Disease |
| title | HNRNPA1-mediated exosomal sorting of miR-483-5p out of renal tubular epithelial cells promotes the progression of diabetic nephropathy-induced renal interstitial fibrosis |
| title_full | HNRNPA1-mediated exosomal sorting of miR-483-5p out of renal tubular epithelial cells promotes the progression of diabetic nephropathy-induced renal interstitial fibrosis |
| title_fullStr | HNRNPA1-mediated exosomal sorting of miR-483-5p out of renal tubular epithelial cells promotes the progression of diabetic nephropathy-induced renal interstitial fibrosis |
| title_full_unstemmed | HNRNPA1-mediated exosomal sorting of miR-483-5p out of renal tubular epithelial cells promotes the progression of diabetic nephropathy-induced renal interstitial fibrosis |
| title_short | HNRNPA1-mediated exosomal sorting of miR-483-5p out of renal tubular epithelial cells promotes the progression of diabetic nephropathy-induced renal interstitial fibrosis |
| title_sort | hnrnpa1 mediated exosomal sorting of mir 483 5p out of renal tubular epithelial cells promotes the progression of diabetic nephropathy induced renal interstitial fibrosis |
| url | https://doi.org/10.1038/s41419-021-03460-x |
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