Spleen Tyrosine Kinase (SYK) in the Progression of Peritoneal Fibrosis Through Activation of the TGF-ß1/Smad3 Signaling Pathway.
Med Sci Monit
; 25: 9346-9356, 2019 Dec 08.
Article
em En
| MEDLINE
| ID: mdl-31812978
ABSTRACT
BACKGROUND Long-term exposure to hypertonic and high glucose in peritoneal dialysis fluid can result in peritoneal fibrosis. Spleen tyrosine kinase (SYK) has a role in inflammation and fibrosis. This study aimed to investigate the role of SYK in an in vivo rat model of peritoneal fibrosis and in rat peritoneal mesothelial cells (PMCs) in vitro and to investigate the underlying mechanisms. MATERIAL AND METHODS Sprague-Dawley rats (N=24) were randomized into the sham control group (N=6); the peritoneal fibrosis group (N=6) treated with intraperitoneal chlorhexidine digluconate; the SYK inhibitor group (N=6), treated with chlorhexidine digluconate and fostamatinib; and the TGF-ß inhibitor group (N=6), treated with chlorhexidine digluconate and LY2109761. The rat model underwent daily intraperitoneal injection with 0.5 ml of 0.1% chlorhexidine digluconate. Rat peritoneal mesothelial cells (PMCs) were cultured in vitro in high glucose. SYK expression was measured by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blot. Enzyme-linked immunosorbent assay (ELISA) and qRT-PCR measured inflammatory mediators. Transforming growth factor-ß1 (TGF-ß1) and Smad3 were detected by Western blot. Short hairpin RNA (shRNA) was used to target the SYK gene. RESULTS SYK was upregulated in the rat model of peritoneal fibrosis and was induced rat PMCs cultured in high glucose. Knockdown of SYK and inhibition of TGF-ß1 significantly reduced fibrosis and inflammation. Findings in the in vivo rat model confirmed that SYK mediated peritoneal fibrosis by regulating TGF-ß1/Smad3 signaling. CONCLUSIONS In a rat model and in rat PMCs, expression of SYK increased peritoneal fibrosis through activation of the TGF-ß1/Smad3 signaling pathway.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fibrose Peritoneal
/
Quinase Syk
Tipo de estudo:
Prognostic_studies
Limite:
Animals
País/Região como assunto:
Asia
Idioma:
En
Revista:
Med Sci Monit
Assunto da revista:
MEDICINA
Ano de publicação:
2019
Tipo de documento:
Article