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Dexmedetomidine Protects Against Kidney Fibrosis in Diabetic Mice by Targeting miR-101-3p-Mediated EndMT

Objective: Our main purpose is to explore the effect and mechanism of Dexmedetomidine (DEX)  in diabetic nephropathy fibrosis. Methods: Diabetic model was established by intraperitoneal injection of streptozotocin (STZ) treated CD-1 mice and high glucose cultured human dermal microvascular endotheli...

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Autores principales: Song, Li, Feng, Songlin, Yu, Hao, Shi, Sen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: SAGE Publications 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8973067/
https://www.ncbi.nlm.nih.gov/pubmed/35370507
http://dx.doi.org/10.1177/15593258221083486
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author Song, Li
Feng, Songlin
Yu, Hao
Shi, Sen
author_facet Song, Li
Feng, Songlin
Yu, Hao
Shi, Sen
author_sort Song, Li
collection PubMed
description Objective: Our main purpose is to explore the effect and mechanism of Dexmedetomidine (DEX)  in diabetic nephropathy fibrosis. Methods: Diabetic model was established by intraperitoneal injection of streptozotocin (STZ) treated CD-1 mice and high glucose cultured human dermal microvascular endothelial cells (HMVECs). Immunofluorescence was used to detect renal endothelial-mesenchymal transition (EndMT); Hematoxylin and Eosin (HE) staining and Masson’s Trichrome Staining (MTS) was used to analyze renal fibrosis; CCK-8 was used to evaluate cell viability; Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to assess the expression of miR-101-3p; Western blots were utilized to judge the protein expression levels of EndMT, extracellular matrix and TGF-β1/Smad3 signal pathway. Results: In this study, we first found that the protective effect of DEX on DN was related to EndMT. DEX alleviated kidney fibrosis by inhibiting EndMT in diabetic CD-1 mice. DEX could also inhibit high glucose-induced HMVECs EndMT. Then, we confirmed that miR-101-3p was the regulatory target of DEX. The expression of miR-101-3p was decreased in diabetic CD-1 mice and high glucose-induced HMVECs. After DEX treatment, the miR-101-3p increased, and the inhibition of miR-101-3p could counteract the protective effect of DEX and aggravate the EndMT. Finally, we found that the TGF- β1/Smad3 signal pathway was involved in the protective effect of DEX on DN. DEX inhibited the activation of TGF-β1/Smad3 signal pathway. On the contrary, inhibiting miR-101-3p promoted the expression of TGF-β1/Smad3. Conclusion: DEX protects kidney fibrosis in diabetic mice by targeting miR-101-3p-mediated EndMT.
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spelling pubmed-89730672022-04-02 Dexmedetomidine Protects Against Kidney Fibrosis in Diabetic Mice by Targeting miR-101-3p-Mediated EndMT Song, Li Feng, Songlin Yu, Hao Shi, Sen Dose Response Original Article Objective: Our main purpose is to explore the effect and mechanism of Dexmedetomidine (DEX)  in diabetic nephropathy fibrosis. Methods: Diabetic model was established by intraperitoneal injection of streptozotocin (STZ) treated CD-1 mice and high glucose cultured human dermal microvascular endothelial cells (HMVECs). Immunofluorescence was used to detect renal endothelial-mesenchymal transition (EndMT); Hematoxylin and Eosin (HE) staining and Masson’s Trichrome Staining (MTS) was used to analyze renal fibrosis; CCK-8 was used to evaluate cell viability; Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to assess the expression of miR-101-3p; Western blots were utilized to judge the protein expression levels of EndMT, extracellular matrix and TGF-β1/Smad3 signal pathway. Results: In this study, we first found that the protective effect of DEX on DN was related to EndMT. DEX alleviated kidney fibrosis by inhibiting EndMT in diabetic CD-1 mice. DEX could also inhibit high glucose-induced HMVECs EndMT. Then, we confirmed that miR-101-3p was the regulatory target of DEX. The expression of miR-101-3p was decreased in diabetic CD-1 mice and high glucose-induced HMVECs. After DEX treatment, the miR-101-3p increased, and the inhibition of miR-101-3p could counteract the protective effect of DEX and aggravate the EndMT. Finally, we found that the TGF- β1/Smad3 signal pathway was involved in the protective effect of DEX on DN. DEX inhibited the activation of TGF-β1/Smad3 signal pathway. On the contrary, inhibiting miR-101-3p promoted the expression of TGF-β1/Smad3. Conclusion: DEX protects kidney fibrosis in diabetic mice by targeting miR-101-3p-mediated EndMT. SAGE Publications 2022-03-30 /pmc/articles/PMC8973067/ /pubmed/35370507 http://dx.doi.org/10.1177/15593258221083486 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by-nc/4.0/This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).
spellingShingle Original Article
Song, Li
Feng, Songlin
Yu, Hao
Shi, Sen
Dexmedetomidine Protects Against Kidney Fibrosis in Diabetic Mice by Targeting miR-101-3p-Mediated EndMT
title Dexmedetomidine Protects Against Kidney Fibrosis in Diabetic Mice by Targeting miR-101-3p-Mediated EndMT
title_full Dexmedetomidine Protects Against Kidney Fibrosis in Diabetic Mice by Targeting miR-101-3p-Mediated EndMT
title_fullStr Dexmedetomidine Protects Against Kidney Fibrosis in Diabetic Mice by Targeting miR-101-3p-Mediated EndMT
title_full_unstemmed Dexmedetomidine Protects Against Kidney Fibrosis in Diabetic Mice by Targeting miR-101-3p-Mediated EndMT
title_short Dexmedetomidine Protects Against Kidney Fibrosis in Diabetic Mice by Targeting miR-101-3p-Mediated EndMT
title_sort dexmedetomidine protects against kidney fibrosis in diabetic mice by targeting mir-101-3p-mediated endmt
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8973067/
https://www.ncbi.nlm.nih.gov/pubmed/35370507
http://dx.doi.org/10.1177/15593258221083486
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