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KMID : 1037120230410020363
The World Journal of Men¡Çs Health
2023 Volume.41 No. 2 p.363 ~ p.372
Myocardin Reverses Hypoxia-Inducible Factor-1¥á Mediated Phenotypic Modulation of Corpus Cavernosum Smooth Muscle Cells in Hypoxia Induced by Cobalt Chloride
Xiongcai Zhou

Chao Luo
Junhong Fan
Guangqian Gao
Tao Wang
Haibo Zhang
Anyang Wei
Abstract
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.
KEYWORD
Hypoxia, Myocardin, Myocytes, smooth muscle, Phenotype
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