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Prostaglandin E2 inhibits transforming growth factor beta 1-mediated induction of collagen alpha 1(I) in hepatic stellate cells.
J Hepatol. 2004 Aug; 41(2):251-8.JH

Abstract

BACKGROUND/AIMS

Cyclooxygenase-2 (COX-2) has been implicated in a number of hepatic stellate cell (HSC) functions but its relationship to transforming growth factor-beta 1 (TGF-beta 1)-mediated fibrogenesis is unknown. We assessed the impact of COX-2 inhibition and PGE(2) on the regulation of TGF-beta 1-stimulated matrix synthesis in an immortalized human HSC line, LX-1 and corroborated these findings in primary stellate cells.

METHODS

Expression of COX-2 was assessed by Western blotting and real time quantitative PCR. The effect of NS398, a selective COX-2 inhibitor, and PGE(2) on TGF-beta 1-mediated fibrogenesis was examined by measuring mRNA levels of collagen alpha1(I). PGE(2) receptor expression was analyzed by RT-PCR.

RESULTS

Under basal conditions, NS398 suppressed PGE(2) synthesis and induced collagen alpha 1(I) whereas exogenous PGE(2) suppressed expression of collagen alpha1(I). TGF-beta 1 induced COX-2 mRNA, COX-2 protein and PGE(2) biosynthesis. Importantly, TGF-beta 1-mediated induction of collagen alpha 1(I) was markedly suppressed by the addition of exogenous PGE(2). All four major PGE(2) receptors were expressed in LX-1 cells.

CONCLUSIONS

These results suggest that COX-2-derived PGE(2) inhibits both basal and TGF-beta 1-mediated induction of collagen synthesis by HSC. Based on these findings, it will be important to determine whether inhibiting COX-derived PGE(2) synthesis alters the progression of liver fibrosis in vivo.

Authors+Show Affiliations

Division of Liver Diseases, Mount Sinai School of Medicine, New York, NY 10029, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

15288474

Citation

Hui, Alex Y., et al. "Prostaglandin E2 Inhibits Transforming Growth Factor Beta 1-mediated Induction of Collagen Alpha 1(I) in Hepatic Stellate Cells." Journal of Hepatology, vol. 41, no. 2, 2004, pp. 251-8.
Hui AY, Dannenberg AJ, Sung JJ, et al. Prostaglandin E2 inhibits transforming growth factor beta 1-mediated induction of collagen alpha 1(I) in hepatic stellate cells. J Hepatol. 2004;41(2):251-8.
Hui, A. Y., Dannenberg, A. J., Sung, J. J., Subbaramaiah, K., Du, B., Olinga, P., & Friedman, S. L. (2004). Prostaglandin E2 inhibits transforming growth factor beta 1-mediated induction of collagen alpha 1(I) in hepatic stellate cells. Journal of Hepatology, 41(2), 251-8.
Hui AY, et al. Prostaglandin E2 Inhibits Transforming Growth Factor Beta 1-mediated Induction of Collagen Alpha 1(I) in Hepatic Stellate Cells. J Hepatol. 2004;41(2):251-8. PubMed PMID: 15288474.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Prostaglandin E2 inhibits transforming growth factor beta 1-mediated induction of collagen alpha 1(I) in hepatic stellate cells. AU - Hui,Alex Y, AU - Dannenberg,Andrew J, AU - Sung,Joseph J Y, AU - Subbaramaiah,Kotha, AU - Du,Baoheng, AU - Olinga,Peter, AU - Friedman,Scott L, PY - 2003/08/13/received PY - 2004/03/28/revised PY - 2004/04/27/accepted PY - 2004/8/4/pubmed PY - 2005/2/11/medline PY - 2004/8/4/entrez SP - 251 EP - 8 JF - Journal of hepatology JO - J Hepatol VL - 41 IS - 2 N2 - BACKGROUND/AIMS: Cyclooxygenase-2 (COX-2) has been implicated in a number of hepatic stellate cell (HSC) functions but its relationship to transforming growth factor-beta 1 (TGF-beta 1)-mediated fibrogenesis is unknown. We assessed the impact of COX-2 inhibition and PGE(2) on the regulation of TGF-beta 1-stimulated matrix synthesis in an immortalized human HSC line, LX-1 and corroborated these findings in primary stellate cells. METHODS: Expression of COX-2 was assessed by Western blotting and real time quantitative PCR. The effect of NS398, a selective COX-2 inhibitor, and PGE(2) on TGF-beta 1-mediated fibrogenesis was examined by measuring mRNA levels of collagen alpha1(I). PGE(2) receptor expression was analyzed by RT-PCR. RESULTS: Under basal conditions, NS398 suppressed PGE(2) synthesis and induced collagen alpha 1(I) whereas exogenous PGE(2) suppressed expression of collagen alpha1(I). TGF-beta 1 induced COX-2 mRNA, COX-2 protein and PGE(2) biosynthesis. Importantly, TGF-beta 1-mediated induction of collagen alpha 1(I) was markedly suppressed by the addition of exogenous PGE(2). All four major PGE(2) receptors were expressed in LX-1 cells. CONCLUSIONS: These results suggest that COX-2-derived PGE(2) inhibits both basal and TGF-beta 1-mediated induction of collagen synthesis by HSC. Based on these findings, it will be important to determine whether inhibiting COX-derived PGE(2) synthesis alters the progression of liver fibrosis in vivo. SN - 0168-8278 UR - https://www.unboundmedicine.com/medline/citation/15288474/Prostaglandin_E2_inhibits_transforming_growth_factor_beta_1_mediated_induction_of_collagen_alpha_1_I__in_hepatic_stellate_cells_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0168827804002302 DB - PRIME DP - Unbound Medicine ER -