Smooth Muscle Cell-Derived Exosomal miR-30a-5p as a Novel Therapeutic Strategy for Erectile Dysfunction in Diabetes Mellitus

Jingyu Song; Peng Hu; Jiaxin Wang; Wenchao Xu; Kai Cui; Tao Wang; Jihong Liu; Yajun Ruan

doi:10.1111/andr.70234

Smooth Muscle Cell-Derived Exosomal miR-30a-5p as a Novel Therapeutic Strategy for Erectile Dysfunction in Diabetes Mellitus

Andrology. 2026 Apr 16. doi: 10.1111/andr.70234. Online ahead of print.

Authors

Jingyu Song^{1

2}, Peng Hu^{1

2}, Jiaxin Wang^{1

2}, Wenchao Xu^{1

2}, Kai Cui^{1

2}, Tao Wang^{1

2}, Jihong Liu^{1

2}, Yajun Ruan^{1

2}

Affiliations

¹ Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
² Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

PMID: 41987693
DOI: 10.1111/andr.70234

Abstract

Background: Erectile dysfunction (ED) affects more than half of male patients with diabetes. Diabetes mellitus-related ED (DMED) remains challenging to manage due to hyperglycemia-induced apoptosis and fibrosis of corpus cavernosum smooth muscle cells (SMCs). Exosomes secreted by normal SMCs (NSMC-EXOs) have emerged as promising therapeutic vectors. This study investigated the therapeutic role and molecular mechanism of NSMC-EXO-carried microRNA-30a-5p (miR-30a-5p) in DMED.

Methods: Erectile function in DMED rats treated with NSMC-EXOs was assessed via electrophysiological testing. Exosomal miRNA profiles were characterized by sequencing, and potential target genes were identified through bioinformatic prediction. The interaction between miR-30a-5p and Calm1 was experimentally validated. Expression levels of miR-30a-5p, Calm1, and markers of apoptosis and fibrosis were examined in vivo and in vitro. MiR-30a-5p mimics and inhibitors were employed to confirm the regulatory mechanism.

Results: Administration of NSMC-EXOs significantly restored erectile function in DMED rats. Sequencing revealed a marked enrichment of miR-30a-5p in NSMC-EXOs compared with exosomes from high-glucose-treated SMCs. Calm1 was identified as a direct target of miR-30a-5p, with involvement in apoptotic and fibrotic signaling pathways. Both in vivo and in vitro studies demonstrated that NSMC-EXO-derived miR-30a-5p was efficiently internalized by SMCs, suppressed Calm1 expression, and inhibited activation of the Calm1-AMPK-JNK and Calm1-CaMK2-TGFβ1 cascades. Consequently, apoptosis and fibrosis of corpus cavernosum tissue under hyperglycemic conditions were alleviated. Importantly, these protective effects were abolished following miR-30a-5p inhibition, underscoring its pivotal role.

Conclusion: NSMC-EXO-derived miR-30a-5p protects against DMED by directly targeting Calm1 and attenuating pro-apoptotic and pro-fibrotic signaling. These findings provide mechanistic insight supporting the development of exosome-based therapeutic approaches for DMED.

Keywords: diabetes mellitus; erectile dysfunction; exosomes; microRNA‐30a‐5p; smooth muscle cell.

Abstract

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