HGF alleviates renal interstitial fibrosis via inhibiting the TGF-ß1/SMAD pathway.
Eur Rev Med Pharmacol Sci
; 22(22): 7621-7627, 2018 11.
Article
em En
| MEDLINE
| ID: mdl-30536302
ABSTRACT
OBJECTIVE:
To study the role of HGF (stem cell growth factor) in renal interstitial fibrosis and to explore its underlying mechanism. MATERIALS ANDMETHODS:
A unilateral ureteral obstruction (UUO) mouse model was first constructed, and kidney samples of mice were then collected. Fibrosis-related indicators in UUO mice kidney were detected by Western blot. The mRNA and protein levels of HGF in UUO mice were detected by quantitative Real-time-polymerase chain reaction (qRT-PCR) and Western blot, respectively. The HGF overexpression mouse model was established by using UUO mice. For in vitro experiments, fibrosis-related indicators and the expression of HGF were detected in transforming growth factor-ß1 (TGF-ß1)-induced NRK-52E cells. Finally, a p-SMAD3 knockdown mouse model was established to confirm whether p-SMAD3 was involved in HGF-regulated renal interstitial fibrosis.RESULTS:
The expression levels of HGF and α-SMA (α-smooth muscle actin) were both significantly increased in UUO mice, while E-cadherin expression was significantly decreased, which were consistent with results of in vitro experiments. Overexpression of HGF remarkably decreased the protein and mRNA levels of α-SMA in fibrotic NRK-52E cells. After overexpression of HGF in UUO mice, α-SMA was remarkably downregulated, whereas E-cadherin was significantly upregulated. Further, results also demonstrated that HGF was upregulated and α-SMA was downregulated after p-SMAD3 knockdown in UUO mice.CONCLUSIONS:
HGF is highly expressed during renal interstitial fibrosis, which may suppress renal interstitial fibrosis by inhibiting the TGF-ß1/SMAD signaling pathway.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
/
Fator de Crescimento de Hepatócito
/
Proteína Smad3
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Fator de Crescimento Transformador beta1
/
Nefrite Intersticial
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Eur Rev Med Pharmacol Sci
Assunto da revista:
FARMACOLOGIA
/
TOXICOLOGIA
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
China
País de publicação:
IT
/
ITALIA
/
ITALY
/
ITÁLIA