Tags

Type your tag names separated by a space and hit enter

Histone deacetylase inhibition suppresses the transforming growth factor beta1-induced epithelial-to-mesenchymal transition in hepatocytes.
Hepatology. 2010 Sep; 52(3):1033-45.Hep

Abstract

Transforming growth factor beta1 (TGFbeta1) plays a crucial role in the induction of the epithelial-to-mesenchymal transition (EMT) in hepatocytes, which contributes to the pathogenesis of liver fibrosis. The inhibition of the TGFbeta1 cascade suppresses EMT and the resultant fibrosis. In this study, we focus on EMT-induced fibrosis in hepatocytes and the epigenetic regulation of the type I collagen gene. Histone acetylation is an important, major epigenetic mechanism that modulates gene transcription. We evaluated the epigenetic regulation of type I collagen in alpha mouse liver 12 hepatocytes (an untransformed mouse cell line) that had undergone EMT after treatment with TGFbeta1. The histone deacetylase inhibitor trichostatin A (TSA) inhibited EMT; this was reflected by the preservation of epithelial markers and function (E-cadherin and albumin). Fibrosis, the ultimate outcome of EMT, was abolished by TSA; this was indicated by the inhibition of type I collagen deposition. TSA exerted its anti-EMT effects by deactivating the mothers against decapentaplegic homolog 3 (Smad3)/Smad4 transcription complex and by interfering with p300, a coactivator of the type I collagen promoter, and preventing its binding to Smad3. TSA also restored Friend leukemia virus integration 1, an inhibitor of the type I collagen gene. TGFbeta1-induced EMT and its inhibition by TSA were replicated in human primary hepatocytes.

CONCLUSION

Histone deacetylase inhibition abrogates TGFbeta1-induced EMT in hepatocytes and reverses EMT-induced fibrosis by epigenetic modulation of type I collagen.

Authors+Show Affiliations

Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20564330

Citation

Kaimori, Aki, et al. "Histone Deacetylase Inhibition Suppresses the Transforming Growth Factor Beta1-induced Epithelial-to-mesenchymal Transition in Hepatocytes." Hepatology (Baltimore, Md.), vol. 52, no. 3, 2010, pp. 1033-45.
Kaimori A, Potter JJ, Choti M, et al. Histone deacetylase inhibition suppresses the transforming growth factor beta1-induced epithelial-to-mesenchymal transition in hepatocytes. Hepatology. 2010;52(3):1033-45.
Kaimori, A., Potter, J. J., Choti, M., Ding, Z., Mezey, E., & Koteish, A. A. (2010). Histone deacetylase inhibition suppresses the transforming growth factor beta1-induced epithelial-to-mesenchymal transition in hepatocytes. Hepatology (Baltimore, Md.), 52(3), 1033-45. https://doi.org/10.1002/hep.23765
Kaimori A, et al. Histone Deacetylase Inhibition Suppresses the Transforming Growth Factor Beta1-induced Epithelial-to-mesenchymal Transition in Hepatocytes. Hepatology. 2010;52(3):1033-45. PubMed PMID: 20564330.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Histone deacetylase inhibition suppresses the transforming growth factor beta1-induced epithelial-to-mesenchymal transition in hepatocytes. AU - Kaimori,Aki, AU - Potter,James J, AU - Choti,Michael, AU - Ding,Zhen, AU - Mezey,Esteban, AU - Koteish,Ayman A, PY - 2010/6/22/entrez PY - 2010/6/22/pubmed PY - 2010/10/12/medline SP - 1033 EP - 45 JF - Hepatology (Baltimore, Md.) JO - Hepatology VL - 52 IS - 3 N2 - UNLABELLED: Transforming growth factor beta1 (TGFbeta1) plays a crucial role in the induction of the epithelial-to-mesenchymal transition (EMT) in hepatocytes, which contributes to the pathogenesis of liver fibrosis. The inhibition of the TGFbeta1 cascade suppresses EMT and the resultant fibrosis. In this study, we focus on EMT-induced fibrosis in hepatocytes and the epigenetic regulation of the type I collagen gene. Histone acetylation is an important, major epigenetic mechanism that modulates gene transcription. We evaluated the epigenetic regulation of type I collagen in alpha mouse liver 12 hepatocytes (an untransformed mouse cell line) that had undergone EMT after treatment with TGFbeta1. The histone deacetylase inhibitor trichostatin A (TSA) inhibited EMT; this was reflected by the preservation of epithelial markers and function (E-cadherin and albumin). Fibrosis, the ultimate outcome of EMT, was abolished by TSA; this was indicated by the inhibition of type I collagen deposition. TSA exerted its anti-EMT effects by deactivating the mothers against decapentaplegic homolog 3 (Smad3)/Smad4 transcription complex and by interfering with p300, a coactivator of the type I collagen promoter, and preventing its binding to Smad3. TSA also restored Friend leukemia virus integration 1, an inhibitor of the type I collagen gene. TGFbeta1-induced EMT and its inhibition by TSA were replicated in human primary hepatocytes. CONCLUSION: Histone deacetylase inhibition abrogates TGFbeta1-induced EMT in hepatocytes and reverses EMT-induced fibrosis by epigenetic modulation of type I collagen. SN - 1527-3350 UR - https://www.unboundmedicine.com/medline/citation/20564330/Histone_deacetylase_inhibition_suppresses_the_transforming_growth_factor_beta1_induced_epithelial_to_mesenchymal_transition_in_hepatocytes_ L2 - https://doi.org/10.1002/hep.23765 DB - PRIME DP - Unbound Medicine ER -