MYPT1 reduction is a pathogenic factor of erectile dysfunction.
Journal
Communications biology
ISSN: 2399-3642
Titre abrégé: Commun Biol
Pays: England
ID NLM: 101719179
Informations de publication
Date de publication:
25 07 2022
25 07 2022
Historique:
received:
16
11
2020
accepted:
14
07
2022
entrez:
25
7
2022
pubmed:
26
7
2022
medline:
28
7
2022
Statut:
epublish
Résumé
Erectile dysfunction (ED) is closely associated with smooth muscle dysfunction, but its underlying mechanisms remains incompletely understood. We here reported that the reduced expression of myosin phosphatase target subunit 1 (MYPT1), the main regulatory unit of myosin light chain phosphatase, was critical for the development of vasculogenic ED. Male MYPT1 knockout mice had reduced fertility and the penises displayed impaired erections as evidenced by reduced intracavernous pressure (ICP). The penile smooth muscles of the knockout mice displayed enhanced response to G-Protein Couple Receptor agonism and depolarization contractility and resistant relaxation. We further identified a natural compound lotusine that increased the MYPT1 expression by inhibiting SIAH1/2 E3 ligases-mediated protein degradation. This compound sufficiently restored the ICP and improved histological characters of the penile artery of Mypt1 haploinsufficiency mice. In diabetic ED mice (db/db), the decreased expression of MYPT1 was measured, and ICP was improved by lotusine treatment. We conclude that the reduction of MYPT1 is the major pathogenic factor of vasculogenic ED. The restoration of MYPT1 by lotusine improved the function of injured penile smooth muscles, and could be a novel strategy for ED therapy.
Identifiants
pubmed: 35879418
doi: 10.1038/s42003-022-03716-y
pii: 10.1038/s42003-022-03716-y
pmc: PMC9314386
doi:
Substances chimiques
Virulence Factors
0
Myosin-Light-Chain Phosphatase
EC 3.1.3.53
Ppp1r12a protein, mouse
EC 3.1.3.53
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
744Informations de copyright
© 2022. The Author(s).
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