KMID : 1037120230410020363
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The World Journal of Men¡Çs Health 2023 Volume.41 No. 2 p.363 ~ p.372
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Myocardin Reverses Hypoxia-Inducible Factor-1¥á Mediated Phenotypic Modulation of Corpus Cavernosum Smooth Muscle Cells in Hypoxia Induced by Cobalt Chloride
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Xiongcai Zhou
Chao Luo Junhong Fan Guangqian Gao Tao Wang Haibo Zhang Anyang Wei
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Abstract
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Purpose: We aimed to investigate the mechanism of phenotypic transformation of corporal cavernosum smooth muscle cells (CCSMCs) under hypoxic conditions in vitro.
Materials and Methods: In this study, a hypoxia model was established using cobalt chloride (CoCl2). CCSMCs were treated with different concentrations of CoCl2 for varying time periods, and cell viability was assessed. Hypoxia-inducible factor-1¥á (HIF-1¥á), myocardin (Myocd) and phenotypic markers were detected in the CCSMCs. We also transfected the CCSMCs with si-HIF-1¥á and Ad-Myocd and evaluated the effects on phenotypic modulation of CCSMCs and the relationship between HIF- 1¥á and Myocd was evaluated.
Results: CoCl2 inhibited the viability of CCSMCs in a dose- and time-dependent manner, and treatment with 300 ¥ìM CoCl2 for 48 hours were the optimal conditions for establishing the hypoxia model. The results showed increased expression levels of HIF-1¥á and osteopontin and decreased Myocd, alpha-smooth muscle actin, and calponin levels in CCSMCs under hypoxia.
HIF-1¥á knockdown reversed hypoxia-induced phenotypic transformation with elevated Myocd expression. Overexpression of Myocd also reversed the effect of hypoxia on the phenotypic switch, but did not affect HIF-1¥á expression.
Conclusions: Our findings showed that HIF-1¥á was involved in the effect of hypoxia induced by CoCl2 on CCSMC phenotypic modulation, and Myocd overexpression could inhibit this process. Thus, Myocd might be a potential therapeutic target for erectile dysfunction under hypoxia or HIF-1¥á activation.
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KEYWORD
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Hypoxia, Myocardin, Myocytes, smooth muscle, Phenotype
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