Y-27632 targeting ROCK1&2 modulates cell growth, fibrosis and epithelial-mesenchymal transition in hyperplastic prostate by inhibiting β-catenin pathway.
Male
rho-Associated Kinases
/ metabolism
Epithelial-Mesenchymal Transition
/ drug effects
Pyridines
/ pharmacology
Animals
Prostatic Hyperplasia
/ pathology
Humans
Cell Proliferation
/ drug effects
Rats
Fibrosis
/ metabolism
beta Catenin
/ metabolism
Amides
/ pharmacology
Apoptosis
/ drug effects
Prostate
/ pathology
Rats, Sprague-Dawley
Signal Transduction
/ drug effects
Disease Models, Animal
Cell Line
Middle Aged
Benign prostatic hyperplasia
Cell growth
Epithelial-mesenchymal transition
Fibrosis
Y-27632
Journal
Molecular biomedicine
ISSN: 2662-8651
Titre abrégé: Mol Biomed
Pays: Singapore
ID NLM: 9918283581406676
Informations de publication
Date de publication:
26 Oct 2024
26 Oct 2024
Historique:
received:
25
05
2024
accepted:
12
10
2024
medline:
26
10
2024
pubmed:
26
10
2024
entrez:
25
10
2024
Statut:
epublish
Résumé
Benign prostatic hyperplasia (BPH) is a prevalent condition affecting the male urinary system, with its molecular mechanisms of pathogenesis remaining unclear. Y-27632, a non-isoform-selective Rho kinase inhibitor, has shown therapeutic potential in various diseases but its effects on static factors and fibrosis in BPH remain unexplored. This study investigated human prostate tissues, human prostate cell lines, and BPH rat model using immunofluorescence, flow cytometry, quantitative reverse transcription polymerase chain reaction, western blotting, and cell counting kit-8. ROCK1 and ROCK2 were significantly up-regulated in BPH tissues, correlating with clinical parameters. Y-27632 targeted the inhibition of ROCK1 & ROCK2 expression and inhibited cell proliferation, fibrosis, epithelial-mesenchymal transition (EMT), while induced cell apoptosis in a dose-dependent manner. Moreover, knockdown of either ROCK isoform inhibited fibrosis and EMT, induced apoptosis, while ROCK overexpression had the opposite effects. ROCK downregulation inhibited the β-catenin signaling pathway (such as C-MYC, Snail and Survivin) and decreased β-catenin protein stability, while inhibiting TGF-β/Smad
Identifiants
pubmed: 39455522
doi: 10.1186/s43556-024-00216-9
pii: 10.1186/s43556-024-00216-9
doi:
Substances chimiques
rho-Associated Kinases
EC 2.7.11.1
Pyridines
0
Y 27632
138381-45-0
beta Catenin
0
ROCK1 protein, human
EC 2.7.11.1
Amides
0
ROCK2 protein, human
EC 2.7.11.1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
52Informations de copyright
© 2024. The Author(s).
Références
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