Kindlin-2 mediates Peyronie's disease through activation of TGF-ß/Smad signaling pathway under the presence of TGF-ß1.
Cell Signal
; 121: 111286, 2024 Sep.
Article
en En
| MEDLINE
| ID: mdl-38977232
ABSTRACT
BACKGROUND:
Peyronie's disease (PD) causes benign plaques or induration in tunica albuginea (TA). Kindlin-2 regulates the TGF-ß1/Smad3 pathway, which accelerates kidney fibrosis. The study is aimed mainly to investigate the impact of Kindlin-2 on PD formation and its signaling pathways, notably the TGF-ß/Smad pathway in the presence of TGF-ß1.METHODS:
In this mouse investigation, adenovirus TGF-ß1 was injected into TA to produce PD. The model was successfully induced 45 days later. Western Blot (WB) and immunohistochemistry (IHC) were utilized to measure Kindlin-2 in PD model tissue. WB and immunofluorescence assays were utilized to confirm the impact of TGF-ß1 on Kindlin-2 levels in vitro. The interaction among Kindlin-2, TßRI, and Smad3 was detected using immunoprecipitation (IP) experiments. We examined how TGF-ß1 affects Smad3 phosphorylation and downstream gene activation process. Finally, Kindlin-2 and the level of tissue fibrosis were examined in PD model.RESULTS:
Kindlin-2 levels were elevated in the TGF-ß1-induced PD model, confirming that TGF-ß1 can increase Kindlin-2 levels in primary PD cells. Moreover, Kindlin-2 mediates Smad3-TßRI interaction, activates p-Smad3, and enhances TGF-ß1 target gene expression. In vivo investigations reveal that Kindlin-2 promotes PD development and tissue fibrosis. The regulatory effects of Kindlin-2 need the presence of TGF-ß1. Tissue fibrosis can be reduced by downregulating Kindlin-2.CONCLUSION:
Kindlin-2 does not directly activate Smad3 to induce tissue fibrosis. Instead, it exerts its effect through the combined influence of TGF-ß1. Inhibiting Kindlin-2 could potentially be a treatment for PD.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Induración Peniana
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Transducción de Señal
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Proteína smad3
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Factor de Crecimiento Transformador beta1
Límite:
Animals
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Humans
/
Male
Idioma:
En
Revista:
Cell Signal
/
Cell. signal
/
Cellular signalling
Año:
2024
Tipo del documento:
Article
País de afiliación:
China