miR‐137 and its target T‐type CaV3.1 channel modulate dedifferentiation and proliferation of cerebrovascular smooth muscle cells in simulated microgravity rats by regulating calcineurin/NFAT pathway
| Autor: | Jin Ma, Ji-Bo Song, Yun-Gang Bai, Jiu-Hua Cheng, Man-Jiang Xie, Bin Zhang, Hong-Zhe Ma, Li Chen |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
NFATC3 Vascular smooth muscle Upstream and downstream (transduction) Myocytes Smooth Muscle Rats Sprague-Dawley 03 medical and health sciences Calcium Channels T-Type 0302 clinical medicine NFAT Pathway microRNA Animals simulated microgravity Cells Cultured Weightlessness Simulation Cell Proliferation NFATC Transcription Factors Chemistry Calcineurin dedifferentiation T-type calcium channel Brain NFAT Cell Differentiation Cell Biology General Medicine Original Articles Cerebral Arteries Cell biology Rats MicroRNAs 030104 developmental biology vascular smooth muscle cells (VSMCs) Gene Expression Regulation 030220 oncology & carcinogenesis cardiovascular system T‐type calcium channel Original Article Signal Transduction |
| Zdroj: | Cell Proliferation |
| ISSN: | 1365-2184 0960-7722 |
| Popis: | Objectives Postflight orthostatic intolerance has been regarded as a major adverse effect after microgravity exposure, in which cerebrovascular adaptation plays a critical role. Our previous finding suggested that dedifferentiation of vascular smooth muscle cells (VSMCs) might be one of the key contributors to cerebrovascular adaptation under simulated microgravity. This study was aimed to confirm this concept and elucidate the underlying mechanisms. Materials and methods Sprague Dawley rats were subjected to 28-day hindlimb-unloading to simulate microgravity exposure. VSMC dedifferentiation was evaluated by ultrastructural analysis and contractile/synthetic maker detection. The role of T-type CaV 3.1 channel was revealed by assessing its blocking effects. MiR-137 was identified as the upstream of CaV 3.1 channel by luciferase assay and investigated by gain/loss-of-function approaches. Calcineurin/nuclear factor of activated T lymphocytes (NFAT) pathway, the downstream of CaV 3.1 channel, was investigated by detecting calcineurin activity and NFAT nuclear translocation. Results Simulated microgravity induced the dedifferentiation and proliferation in rat cerebral VSMCs. T-type CaV 3.1 channel promoted the dedifferentiation and proliferation of VSMC. MiR-137 and calcineurin/NFATc3 pathway were the upstream and downstream signalling of T-type CaV 3.1 channel in modulating the dedifferentiation and proliferation of VSMCs, respectively. Conclusions The present work demonstrated that miR-137 and its target T-type CaV 3.1 channel modulate the dedifferentiation and proliferation of rat cerebral VSMCs under simulated microgravity by regulating calcineurin/NFATc3 pathway. |
| Databáze: | OpenAIRE |
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