Circulating exosomal miR-16-5p and let-7e-5p are associated with bladder fibrosis of diabetic cystopathy

Abstract Diabetic cystopathy (DCP) is a prevalent etiology of bladder dysfunction in individuals with longstanding diabetes, frequently leading to bladder interstitial fibrosis. Research investigating the initial pathological alterations of DCP is notably scarce. To comprehend the development of fib...

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Main Authors: Bo Xue, Gaohaer Kadeerhan, Li-bin Sun, Yong-quan Chen, Xiao-feng Hu, Zi-kuan Zhang, Dong-wen Wang
Format: Article
Language:English
Published: Nature Portfolio 2024-01-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-024-51451-7
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author Bo Xue
Gaohaer Kadeerhan
Li-bin Sun
Yong-quan Chen
Xiao-feng Hu
Zi-kuan Zhang
Dong-wen Wang
author_facet Bo Xue
Gaohaer Kadeerhan
Li-bin Sun
Yong-quan Chen
Xiao-feng Hu
Zi-kuan Zhang
Dong-wen Wang
author_sort Bo Xue
collection DOAJ
description Abstract Diabetic cystopathy (DCP) is a prevalent etiology of bladder dysfunction in individuals with longstanding diabetes, frequently leading to bladder interstitial fibrosis. Research investigating the initial pathological alterations of DCP is notably scarce. To comprehend the development of fibrosis and find effective biomarkers for its diagnosis, we prepared streptozotocin-induced long-term diabetic SD rats exhibiting a type 1 diabetes phenotype and bladder fibrosis in histology detection. After observing myofibroblast differentiation from rats’ primary bladder fibroblasts with immunofluorescence, we isolated fibroblasts derived exosomes and performed exosomal miRNA sequencing. The co-differentially expressed miRNAs (DEMis) (miR-16-5p and let-7e-5p) were screened through a joint analysis of diabetic rats and long-term patients’ plasma data (GES97123) downloaded from the GEO database. Then two co-DEMis were validated by quantitative PCR on exosomes derived from diabetic rats’ plasma. Following with a series of analysis, including target mRNAs and transcription factors (TFs) prediction, hubgenes identification, protein–protein interaction (PPI) network construction and gene enrichment analysis, a miRNA-mediated genetic regulatory network consisting of two miRNAs, nine TFs, and thirty target mRNAs were identified in relation to fibrotic processes. Thus, circulating exosomal miR-16-5p and let-7e-5p are associated with bladder fibrosis of DCP, and the crucial genes in regulatory network might hold immense significance in studying the pathogenesis and molecular mechanisms of fibrosis, which deserves further exploration.
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spelling doaj.art-a71d93d0816d4e5ca6c09ec826cc4c202024-01-14T12:20:11ZengNature PortfolioScientific Reports2045-23222024-01-0114111610.1038/s41598-024-51451-7Circulating exosomal miR-16-5p and let-7e-5p are associated with bladder fibrosis of diabetic cystopathyBo Xue0Gaohaer Kadeerhan1Li-bin Sun2Yong-quan Chen3Xiao-feng Hu4Zi-kuan Zhang5Dong-wen Wang6Shanxi Medical UniversityDepartment of Urology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeShanxi Medical UniversityShanxi Medical UniversityShanxi Medical UniversityShanxi Medical UniversityShanxi Medical UniversityAbstract Diabetic cystopathy (DCP) is a prevalent etiology of bladder dysfunction in individuals with longstanding diabetes, frequently leading to bladder interstitial fibrosis. Research investigating the initial pathological alterations of DCP is notably scarce. To comprehend the development of fibrosis and find effective biomarkers for its diagnosis, we prepared streptozotocin-induced long-term diabetic SD rats exhibiting a type 1 diabetes phenotype and bladder fibrosis in histology detection. After observing myofibroblast differentiation from rats’ primary bladder fibroblasts with immunofluorescence, we isolated fibroblasts derived exosomes and performed exosomal miRNA sequencing. The co-differentially expressed miRNAs (DEMis) (miR-16-5p and let-7e-5p) were screened through a joint analysis of diabetic rats and long-term patients’ plasma data (GES97123) downloaded from the GEO database. Then two co-DEMis were validated by quantitative PCR on exosomes derived from diabetic rats’ plasma. Following with a series of analysis, including target mRNAs and transcription factors (TFs) prediction, hubgenes identification, protein–protein interaction (PPI) network construction and gene enrichment analysis, a miRNA-mediated genetic regulatory network consisting of two miRNAs, nine TFs, and thirty target mRNAs were identified in relation to fibrotic processes. Thus, circulating exosomal miR-16-5p and let-7e-5p are associated with bladder fibrosis of DCP, and the crucial genes in regulatory network might hold immense significance in studying the pathogenesis and molecular mechanisms of fibrosis, which deserves further exploration.https://doi.org/10.1038/s41598-024-51451-7
spellingShingle Bo Xue
Gaohaer Kadeerhan
Li-bin Sun
Yong-quan Chen
Xiao-feng Hu
Zi-kuan Zhang
Dong-wen Wang
Circulating exosomal miR-16-5p and let-7e-5p are associated with bladder fibrosis of diabetic cystopathy
Scientific Reports
title Circulating exosomal miR-16-5p and let-7e-5p are associated with bladder fibrosis of diabetic cystopathy
title_full Circulating exosomal miR-16-5p and let-7e-5p are associated with bladder fibrosis of diabetic cystopathy
title_fullStr Circulating exosomal miR-16-5p and let-7e-5p are associated with bladder fibrosis of diabetic cystopathy
title_full_unstemmed Circulating exosomal miR-16-5p and let-7e-5p are associated with bladder fibrosis of diabetic cystopathy
title_short Circulating exosomal miR-16-5p and let-7e-5p are associated with bladder fibrosis of diabetic cystopathy
title_sort circulating exosomal mir 16 5p and let 7e 5p are associated with bladder fibrosis of diabetic cystopathy
url https://doi.org/10.1038/s41598-024-51451-7
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