| | |  | | | | Record from Web of Science® | | | | | | |
| Activated human hepatic stellate cells express the renin-angiotensin system and synthesize angiotensin II |
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| Author(s): Bataller R, Sancho-Bru P, Gines P, Lora JM, Al-Garawi A, Sole M, Colmenero J, Nicolas JM, Jimenez W, Weich N, Gutierrez-Ramos JC, Arroyo V, Rodes J |
| Source: GASTROENTEROLOGY Volume: 125 Issue: 1 Pages: 117-125 Published: JUL 2003 |
| Times Cited: 96 References: 37 |
| Abstract: Background & Aims: The renin-angiotensin system plays an important role in hepatic fibrogenesis. In other organs, myofibroblasts accumulated in damaged tissues generate angiotensin II, which promotes inflammation and extracellular matrix synthesis. It is unknown whether myofibroblastic hepatic stellate cells, the main hepatic fibrogenic cell type, express the renin-angiotensin system and synthesize angiotensin II. The aim of this study was to investigate whether quiescent and activated human hepatic stellate cells contain the components of the renin-angiotensin system and synthesize angiotensin II. Methods: Hepatic stellate cells were freshly isolated from normal human livers (quiescent hepatic stellate cells) and from human cirrhotic livers (in vivo activated hepatic stellate cells). Culture-activated hepatic stellate cells were used after a second passage of quiescent hepatic stellate cells. Angiotensinogen, renin, and angiotensin-converting enzyme were assessed by quantitative polymerase chain reaction. Angiotensin II production was assessed by enzyme-linked immunosorbent assay and immunohistochemistry, Results: Quiescent hepatic stellate cells barely express the reninangiotensin system components-angiotensinogen, renin, and angiotensin-converting enzyme-and do not secrete angiotensin II In contrast, both in vivo activated hepatic stellate cells and culture-activated hepatic stellate cells highly express active renin and angiotensin-converting enzyme and secrete angiotensin II to the culture media. Mature angiotensin II protein is also detected in the cytoplasm of in vivo activated and culture-activated hepatic stellate cells. Growth factors (platelet-derived growth factor and epidermal growth factor) and vasoconstrictor substances (endothelin-1 and thrombin) stimulate angiotensin II synthesis, whereas transforming growth factor-beta and proinflammatory cytokines have no effect. Vasodilator substances markedly attenuate the effect of endothelin-1. Conclusions: After activation, human hepatic stellate cells express the components of the renin-angiotensin system and synthesize angiotensin II. These results suggest that locally generated angiotensin II could participate in tissue remodeling in the human liver. |
| Document Type: Article |
| Language: English |
| Reprint Address: Gines, P (reprint author), Univ Barcelona, Liver Unit, Hosp Clin Barcelona,Sch Med, Dept Med,Inst Invest Biomed August Pi & Sunyer, Villarroel 170, E-08036 Barcelona, Catalonia Spain |
Addresses:
1. Univ Barcelona, Liver Unit, Hosp Clin Barcelona,Sch Med, Dept Med,Inst Invest Biomed August Pi & Sunyer, E-08036 Barcelona, Catalonia Spain
2. Inst Reina Sofia Invest Nefrol, Barcelona, Spain
3. Millennium Pharmaceut Inc, Immunol Sect, Cambridge, MA USA
4. Univ Barcelona, Pathol Unit, Hosp Clin Barcelona,Sch Med, Dept Med,Inst Invest Biomed August Pi & Sunyer, E-08036 Barcelona, Catalonia Spain
5. Univ Barcelona, Gen Internal Med Unit, Hosp Clin Barcelona,Sch Med, Dept Med,Inst Invest Biomed August Pi & Sunyer, E-08036 Barcelona, Catalonia Spain
6. Univ Barcelona, Hormonol Unit, Hosp Clin Barcelona,Sch Med, Dept Med,Inst Invest Biomed August Pi & Sunyer, E-08036 Barcelona, Catalonia Spain |
| Publisher: W B SAUNDERS CO, INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA |
| Subject Category: Gastroenterology & Hepatology |
| IDS Number: 699GH |
| ISSN: 0016-5085 |
| DOI: 10.1016/S0016-5085(03)00695-4 |
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