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ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Cardiovascular and Smooth Muscle Pharmacology
Volume 15 - 2024 |
doi: 10.3389/fphar.2024.1436013
Inhibition of the RIP3/MLKL/TRPM7 necroptotic pathway ameliorates diabetes mellitus-induced erectile dysfunction by reducing cell death, fibrosis, and inflammation
Provisionally accepted- Xinjiang Medical University, Ürümqi, China
Diabetes mellitus-induced erectile dysfunction (DMED) is a common complication in patients with diabetes mellitus. Necroptosis is regarded as a form of cell death that is intimately associated with the inflammatory response, which is not only initiated by inflammatory factors such as TNF-α, but also triggers the inflammatory cascade through the rupture of the dying cell. There is no definitive study on the role of necroptosis in the the pathological process of DMED. In light of the pathological features of high inflammation levels in DMED patients, we hypothesise that necroptosis may play an important role in the course of DMED. Our study found that the penile tissues of DMED rats showed high levels of necroptosis. Furthermore, the inhibition of necroptosis with a receptor-interacting protein kinase 3 (RIP3) inhibitor or Yimusake (a common herbal remedy for ED) rescued damage to corpus cavernosum smooth muscle cells (CCSMC) under high glucose conditions. Mechanistically, in vivo experiments have demonstrated that RIP3 can recruit and promote mixed lineage kinase domain like protein (MLKL) phosphorylation, leading to the activation of transient receptor potential melastatin 7 (TRPM7) and triggering *
Keywords: necroptosis, RIP3/MLKL/TRPM7, Corpus cavernosum smooth muscle cells, Diabetes mellitus-induced erectile dysfunction, RIP3 inhibitor, Yimusake
Received: 21 May 2024; Accepted: 03 Sep 2024.
Copyright: © 2024 Niu, Yang, Zhu, Jin, Yang, Zhang, Liu, Zhang and Fengxia. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Liu Fengxia, Xinjiang Medical University, Ürümqi, China
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