Loss of steroid receptor co-activator-3 attenuates carbon tetrachloride-induced murine hepatic injury and fibrosis
Ma, X; Xu, L; Wang, S; Chen, H; Xu, J; Li, X; Ning, G
HERO ID
3484986
Reference Type
Journal Article
Year
2009
Language
English
PMID
| HERO ID | 3484986 |
|---|---|
| In Press | No |
| Year | 2009 |
| Title | Loss of steroid receptor co-activator-3 attenuates carbon tetrachloride-induced murine hepatic injury and fibrosis |
| Authors | Ma, X; Xu, L; Wang, S; Chen, H; Xu, J; Li, X; Ning, G |
| Journal | Laboratory Investigation |
| Volume | 89 |
| Issue | 8 |
| Page Numbers | 903-914 |
| Abstract | Hepatic fibrosis, a disease characterized by altered accumulation of extracellular matrix, can cause cirrhosis and liver failure. There is growing interest in the impact of co-activators on hepatic fibrogenesis. Here, we provided genetic evidence that mice lacking steroid receptor co-activator-3 (SRC-3) were protected against carbon tetrachloride (CCl4)-induced acute liver necrosis and chronic hepatic fibrosis. After acute CCl4 treatment, SRC-3(-/-) mice showed attenuated profibrotic response and hepatocyte apoptosis, whereas hepatocyte proliferation was elevated in SRC-3(-/-) mice versus SRC-3+/+ mice. Similarly, chronically CCl4-treated SRC-3(-/-) mice showed significant weakening of inflammatory infiltrates, hepatic stellate cell activation and collagen accumulation in the liver compared with SRC-3+/+ mice. Further investigation revealed that TGFbeta1/Smad signaling pathway was impaired in the absence of SRC-3. Moreover, the expression levels of SRC-3, as assessed in human tissue microarray of liver diseases, correlated positively with degrees of fibrosis. These data revealed that SRC-3(-/-) mice were resistant to CCl4-induced acute and chronic hepatic damage and TGFbeta1/Smad signaling was suppressed in the lack of SRC-3. Our results established an essential involvement of SRC-3 in liver fibrogenesis, which might provide new clues to the future treatment of hepatic fibrosis. |
| Doi | 10.1038/labinvest.2009.51 |
| Pmid | 19488034 |
| Is Certified Translation | No |
| Dupe Override | No |
| Is Public | Yes |
| Language Text | English |