Hypoxia-Induced Phenotypic Transformation of Corpus Cavernosum Smooth Muscle Cells After Cavernous Nerve Crush Injury by Down-Regulating P38 Mitogen-Activated Protein Kinase Expression

Abstract

Introduction: Cavernosal nerve (CN) injury is commonly caused by radical prostatectomy surgery, and it might directly lead to erectile dysfunction (ED). Currently, the role of mitogen-activated protein kinase (MAPK) family proteins in phenotypic transformation of corpus cavernosum smooth muscle cell (CCSMC) after CNs injury is poorly understood. Aim: To investigate the role of p38 MAPK in hypoxia-induced phenotypic transformation of CCSMCs after CN injury. Methods: In total, 20 SpragueeDawley rats (male and 8 weeks of age) were randomly divided into 2 groups, including a sham group and CNCI group. In the sham group, rats were sham-operated by identifying 2 CNs without causing direct damage to the CNs. In the CNCI group, rats were subjected to bilateral CN crush injury. CCSMCs were isolated from the normal corpus cavernosum tissues of the SpragueeDawley rat and then cultured in 21% or 1% O 2 concentration context for 48 hours. Main Outcome Measures: Intracavernous pressure/mean arterial pressure were analyzed to measure erectile response. The impact of hypoxia on penile pathology, as well as the expression of extracellular signal-regulated kinases, the c-Jun NH2-terminal kinase, and p38 MAPK, were analyzed. Results: Compared with the sham group, the intracavernous pressure/mean arterial pressure rate and a-smooth muscle actin expression of CNCI group were decreased significantly (P ¼ .0001; P ¼ .016, respectively), but vimentin expression was significantly increased (P ¼ .023). Phosphorylated p38 level in CNCI group was decreased significantly (P ¼ .017; sham: 0.17 ± 0.005; CNCI: 0.14 ± 0.02). The CCSMCs in the normoxia group were long fusiform, whereas the morphology of CCSMCs in the hypoxia group became hypertrophic. After hypoxia for 48 hours, the expression of a-smooth muscle actin and phosphorylated p38 MAPK was decreased significantly (P ¼ .01; P ¼ .024, normoxia: 0.66 ± 0.18, hypoxia: 0.26 ± 0.08, respectively), and the expression of hypoxia-inducible factor-1a and collagen I was increased significantly in hypoxia group (P ¼ .04; P ¼ .012, respectively). Conclusions: Hypoxia induced the phenotypic transformation of CCSMCs after CNCI might be associated with the downregulation of phosphorylated p38 MAPK. Chen S, Huang X, Kong X, et al. Hypoxia-Induced

Role of mechanotransduction mediated by YAP/TAZ in the treatment of neurogenic erectile dysfunction with low‐intensity pulsed ultrasound

“…Unlike the findings of Chen et al. in a study of neurologically injured rats, 36 in the present experiment, we found by RT–qPCR and Western blot that in the BCNI group of rats, at both 14 and 28 days, the phosphorylation level of p38 MAPK was elevated, and this change was partially reversed after LIPUS treatment. Therefore, we can reasonably speculate that p38 MAPK is a potential upstream regulatory signal of YAP/TAZ that regulates the general mechanism of penile tissue repair after injury.…”

3D reconstruction and histopathological analyses on murine corporal body

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Micro RNA 200a contributes to the smooth muscle cells growth in aged‐related erectile dysfunction via regulating Rho/ ROCK pathway

“…The cells used in the experiments were all within 4 passages. The method of primary cell culture has already been described (Chen et al, 2019).…”