Adipose stem cells ameliorate erectile dysfunction in diabetes mellitus rats by attenuating ferroptosis through NRP1 with SLC7A11 interaction

Abstract

Background

Adipose stem cells (ADSCs) have garneVred increasing attention for their potential to treat diabetes mellitus erectile dysfunction (DMED), but the underlying molecular mechanisms remain unclear. The aim of this study was to identify and investigate the key cytokines and mechanisms by which ADSCs improve erectile function in DMED rats.

Methods

We performed in vivo and in vitro assays, including rat erectile function assessment, cell co-culture, cytokine microarray screening and co-immunoprecipitation to investigate the role of ADSCs in improving erectile function in DMED rats.

Results

Our analyses confirmed the occurrence of ferroptosis in the corpus cavernosum of DMED rats, while ADSCs treatment significantly restored erectile function and improved relevant indicators of ferroptosis. In vitro assays further indicated that corpus cavernosum smooth muscle cells (CCSMCs) co-cultured with ADSCs exhibited enhanced resistance to ferroptosis, with notably lower levels of cytoplasmic and lipid reactive oxygen species compared to the ferroptosis inducer Erastin-treated group. Mechanistic studies revealed that Neuropilin 1 (NRP1) may be a key molecule in ADSCs to improve erectile function in DMED rats. Furthermore, NRP1 in CCSMCs can interact with solute carrier family 7 member 11 (SLC7A11) to enhance the function of the glutamate-cysteine countertransport (Xc-) system and ferroptosis resistance in CCSMCs.

Conclusion

In conclusion, our findings indicate that NRP1 is a key molecule for ADSCs treatment to alleviate ferroptosis and improve erectile function in DMED rats, providing a promising target for DMED treatment and prognosis.