Nesfatin-1 regulates the phenotype transition of cavernous smooth muscle cells by activating PI3K/AKT/mTOR signaling pathway to improve diabetic erectile dysfunction
Keming Chen,
Bincheng Huang,
Jiajing Feng,
Shuzhe Fan,
Zhengxing Hu,
Shuai Ren,
Haifu Tian,
A.L.-QAISIMOHAMMED Abdulkarem,
Xuehao Wang,
Yunshang Tuo,
Xiaoxia Liang,
Haibo Xie,
Rui He,
Guangyong Li
Affiliations
Keming Chen
Urology Department of General Hospital, Ningxia Medical University, Ningxia 750000, China; Key Laboratory of Fertility Preservation and Maintenance of Ministry of Education, Ningxia Medical University, Yinchuan, China
Bincheng Huang
Urology Department of General Hospital, Ningxia Medical University, Ningxia 750000, China; Key Laboratory of Fertility Preservation and Maintenance of Ministry of Education, Ningxia Medical University, Yinchuan, China
Jiajing Feng
Urology Department of General Hospital, Ningxia Medical University, Ningxia 750000, China
Shuzhe Fan
School of traditional chinese medicine NingxiaMedicalUniversity,Yinchuan, China
Zhengxing Hu
Urology Department of General Hospital, Ningxia Medical University, Ningxia 750000, China
Shuai Ren
Urology Department of General Hospital, Ningxia Medical University, Ningxia 750000, China
Haifu Tian
Urology Department of General Hospital, Ningxia Medical University, Ningxia 750000, China
A.L.-QAISIMOHAMMED Abdulkarem
Urology Department of General Hospital, Ningxia Medical University, Ningxia 750000, China
Xuehao Wang
Urology Department of General Hospital, Ningxia Medical University, Ningxia 750000, China
Yunshang Tuo
Urology Department of General Hospital, Ningxia Medical University, Ningxia 750000, China
Xiaoxia Liang
Key Laboratory of Fertility Preservation and Maintenance of Ministry of Education, Ningxia Medical University, Yinchuan, China
Haibo Xie
Key Laboratory of Fertility Preservation and Maintenance of Ministry of Education, Ningxia Medical University, Yinchuan, China
Rui He
Key Laboratory of Fertility Preservation and Maintenance of Ministry of Education, Ningxia Medical University, Yinchuan, China; Corresponding author.
Guangyong Li
Urology Department of General Hospital, Ningxia Medical University, Ningxia 750000, China; Corresponding author.
Objective: This study aims to explore the impact of Nesfatin-1 on type 2 diabetic erectile dysfunction (T2DMED) and its underlying mechanism in regulating the phenotypic switching of corpus cavernosum smooth muscle cells (CCSMCs). Methods: Twenty-four 4-week-old male C57 wild-type mice were randomly assigned to the control group, model group, and Nesfatin-1 treatment group. Monitoring included body weight, blood glucose levels, and penile cavernous pressure (ICP). Histochemistry and Western blot analyses were conducted to assess the expressions of α-SMA, OPN, and factors related to the PI3K/AKT/mTOR signaling pathway. CCSMCs were categorized into the control group, high glucose and high oleic acid group (GO group), Nesfatin-1 treatment group (GO + N group), sildenafil positive control group (GO + S group), and PI3K inhibitor group (GO + N + E group). Changes in phenotypic markers, cell morphology, and the PI3K/AKT/mTOR signaling pathway were observed in each group. Results: (1) Nesfatin-1 significantly ameliorated the body size, body weight, blood glucose, glucose tolerance, and insulin resistance in T2DMED mice. (2) Following Nesfatin-1 treatment, the ICP/MSBP ratio and the peak of the ICP curve demonstrated a significant increase. (3) Nesfatin-1 significantly enhanced smooth muscle and reduced collagen fibers in the corpus cavernosum. (4) Nesfatin-1 notably increased α-SMA expression and decreased OPN expression in CCSMCs. (5) Nesfatin-1 elevated PI3K, p-AKT/AKT, and p-mTOR/mTOR levels in penile cavernous tissue. Conclusions: Nesfatin-1 not only effectively improves body weight and blood glucose levels in diabetic mice but also enhances erectile function and regulates the phenotypic switching of corpus cavernosum smooth muscle. The potential mechanism involves Nesfatin-1 activating the PI3K/AKT/mTOR signaling pathway to induce the conversion of CCSMCs to a contractile phenotype.
