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Absence of hepatic stellate cell retinoid lipid droplets does not enhance hepatic fibrosis but decreases hepatic carcinogenesis

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Absence of hepatic stellate cell retinoid lipid droplets does not enhance hepatic fibrosis but decreases hepatic carcinogenesis. / Kluwe, Johannes; Wongsiriroj, Nuttaporn; Troeger, Juliane S; Gwak, Geum-Youn; Dapito, Dianne H; Pradere, Jean-Philippe; Jiang, Hongfeng; Siddiqi, Maham; Piantedosi, Roseann; O'Byrne, Sheila M; Blaner, William S; Schwabe, Robert F.

in: GUT, Jahrgang 60, Nr. 9, 09.2011, S. 1260-8.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Kluwe, J, Wongsiriroj, N, Troeger, JS, Gwak, G-Y, Dapito, DH, Pradere, J-P, Jiang, H, Siddiqi, M, Piantedosi, R, O'Byrne, SM, Blaner, WS & Schwabe, RF 2011, 'Absence of hepatic stellate cell retinoid lipid droplets does not enhance hepatic fibrosis but decreases hepatic carcinogenesis', GUT, Jg. 60, Nr. 9, S. 1260-8. https://doi.org/10.1136/gut.2010.209551

APA

Kluwe, J., Wongsiriroj, N., Troeger, J. S., Gwak, G-Y., Dapito, D. H., Pradere, J-P., Jiang, H., Siddiqi, M., Piantedosi, R., O'Byrne, S. M., Blaner, W. S., & Schwabe, R. F. (2011). Absence of hepatic stellate cell retinoid lipid droplets does not enhance hepatic fibrosis but decreases hepatic carcinogenesis. GUT, 60(9), 1260-8. https://doi.org/10.1136/gut.2010.209551

Vancouver

Kluwe J, Wongsiriroj N, Troeger JS, Gwak G-Y, Dapito DH, Pradere J-P et al. Absence of hepatic stellate cell retinoid lipid droplets does not enhance hepatic fibrosis but decreases hepatic carcinogenesis. GUT. 2011 Sep;60(9):1260-8. https://doi.org/10.1136/gut.2010.209551

Bibtex

@article{a5b9c54eccce4c6d84d451e49292487f,
title = "Absence of hepatic stellate cell retinoid lipid droplets does not enhance hepatic fibrosis but decreases hepatic carcinogenesis",
abstract = "OBJECTIVE: Hepatic stellate cells (HSCs) contain a number of bioactive metabolites or their precursors including retinoids in their characteristic lipid droplets. The loss of lipid droplets and retinoids is a hallmark of HSC activation, but it remains unclear whether this loss promotes HSC activation, liver fibrogenesis or carcinogenesis.DESIGN: Spontaneous and experimental fibrogenesis as well as a diethylnitrosamine-induced hepatocarcinogenesis were investigated in lecithin-retinol acyltransferase (LRAT)-deficient mice which lack retinoid-containing lipids droplets in their HSCs.RESULTS: Following HSC activation, LRAT expression was rapidly lost, emphasising its importance in lipid droplet biology in HSCs. Surprisingly, there was no difference in fibrosis induced by bile duct ligation (BDL) or by eight injections of carbon tetrachloride (CCl4) between wild-type and LRAT-deficient mice. To exclude the possibility that the effects on fibrogenesis were missed due to the rapid downregulation of LRAT following HSC activation, acute as well as spontaneous liver fibrosis was investigated. However, there was no increased fibrosis in 3-, 8- and 12-month-old LRAT-deficient mice and in LRAT-deficient mice after a single injection of CCl4 compared with wild-type mice. To determine whether the absence of retinoids in HSCs affects hepatocarcinogenesis, wild-type and LRAT-deficient mice were injected with diethylnitrosamine. LRAT deficiency decreased diethylnitrosamine-induced injury and tumour load and increased the expression of the retinoic acid responsive genes Cyp26a1, RARb and p21, suggesting that the lower tumour load of LRAT-deficient mice was a result of increased retinoid signalling and subsequent p21-mediated inhibition of proliferation.CONCLUSIONS: The absence of retinoid-containing HSC lipid droplets does not promote HSC activation but reduces hepatocarcinogenesis.",
keywords = "Acyltransferases, Animals, Carbon Tetrachloride, Cell Transformation, Neoplastic, Cells, Cultured, Diethylnitrosamine, Down-Regulation, Hepatic Stellate Cells, Liver Cirrhosis, Liver Neoplasms, Experimental, Male, Mice, Mice, Inbred C57BL",
author = "Johannes Kluwe and Nuttaporn Wongsiriroj and Troeger, {Juliane S} and Geum-Youn Gwak and Dapito, {Dianne H} and Jean-Philippe Pradere and Hongfeng Jiang and Maham Siddiqi and Roseann Piantedosi and O'Byrne, {Sheila M} and Blaner, {William S} and Schwabe, {Robert F}",
year = "2011",
month = sep,
doi = "10.1136/gut.2010.209551",
language = "English",
volume = "60",
pages = "1260--8",
journal = "GUT",
issn = "0017-5749",
publisher = "BMJ PUBLISHING GROUP",
number = "9",

}

RIS

TY - JOUR

T1 - Absence of hepatic stellate cell retinoid lipid droplets does not enhance hepatic fibrosis but decreases hepatic carcinogenesis

AU - Kluwe, Johannes

AU - Wongsiriroj, Nuttaporn

AU - Troeger, Juliane S

AU - Gwak, Geum-Youn

AU - Dapito, Dianne H

AU - Pradere, Jean-Philippe

AU - Jiang, Hongfeng

AU - Siddiqi, Maham

AU - Piantedosi, Roseann

AU - O'Byrne, Sheila M

AU - Blaner, William S

AU - Schwabe, Robert F

PY - 2011/9

Y1 - 2011/9

N2 - OBJECTIVE: Hepatic stellate cells (HSCs) contain a number of bioactive metabolites or their precursors including retinoids in their characteristic lipid droplets. The loss of lipid droplets and retinoids is a hallmark of HSC activation, but it remains unclear whether this loss promotes HSC activation, liver fibrogenesis or carcinogenesis.DESIGN: Spontaneous and experimental fibrogenesis as well as a diethylnitrosamine-induced hepatocarcinogenesis were investigated in lecithin-retinol acyltransferase (LRAT)-deficient mice which lack retinoid-containing lipids droplets in their HSCs.RESULTS: Following HSC activation, LRAT expression was rapidly lost, emphasising its importance in lipid droplet biology in HSCs. Surprisingly, there was no difference in fibrosis induced by bile duct ligation (BDL) or by eight injections of carbon tetrachloride (CCl4) between wild-type and LRAT-deficient mice. To exclude the possibility that the effects on fibrogenesis were missed due to the rapid downregulation of LRAT following HSC activation, acute as well as spontaneous liver fibrosis was investigated. However, there was no increased fibrosis in 3-, 8- and 12-month-old LRAT-deficient mice and in LRAT-deficient mice after a single injection of CCl4 compared with wild-type mice. To determine whether the absence of retinoids in HSCs affects hepatocarcinogenesis, wild-type and LRAT-deficient mice were injected with diethylnitrosamine. LRAT deficiency decreased diethylnitrosamine-induced injury and tumour load and increased the expression of the retinoic acid responsive genes Cyp26a1, RARb and p21, suggesting that the lower tumour load of LRAT-deficient mice was a result of increased retinoid signalling and subsequent p21-mediated inhibition of proliferation.CONCLUSIONS: The absence of retinoid-containing HSC lipid droplets does not promote HSC activation but reduces hepatocarcinogenesis.

AB - OBJECTIVE: Hepatic stellate cells (HSCs) contain a number of bioactive metabolites or their precursors including retinoids in their characteristic lipid droplets. The loss of lipid droplets and retinoids is a hallmark of HSC activation, but it remains unclear whether this loss promotes HSC activation, liver fibrogenesis or carcinogenesis.DESIGN: Spontaneous and experimental fibrogenesis as well as a diethylnitrosamine-induced hepatocarcinogenesis were investigated in lecithin-retinol acyltransferase (LRAT)-deficient mice which lack retinoid-containing lipids droplets in their HSCs.RESULTS: Following HSC activation, LRAT expression was rapidly lost, emphasising its importance in lipid droplet biology in HSCs. Surprisingly, there was no difference in fibrosis induced by bile duct ligation (BDL) or by eight injections of carbon tetrachloride (CCl4) between wild-type and LRAT-deficient mice. To exclude the possibility that the effects on fibrogenesis were missed due to the rapid downregulation of LRAT following HSC activation, acute as well as spontaneous liver fibrosis was investigated. However, there was no increased fibrosis in 3-, 8- and 12-month-old LRAT-deficient mice and in LRAT-deficient mice after a single injection of CCl4 compared with wild-type mice. To determine whether the absence of retinoids in HSCs affects hepatocarcinogenesis, wild-type and LRAT-deficient mice were injected with diethylnitrosamine. LRAT deficiency decreased diethylnitrosamine-induced injury and tumour load and increased the expression of the retinoic acid responsive genes Cyp26a1, RARb and p21, suggesting that the lower tumour load of LRAT-deficient mice was a result of increased retinoid signalling and subsequent p21-mediated inhibition of proliferation.CONCLUSIONS: The absence of retinoid-containing HSC lipid droplets does not promote HSC activation but reduces hepatocarcinogenesis.

KW - Acyltransferases

KW - Animals

KW - Carbon Tetrachloride

KW - Cell Transformation, Neoplastic

KW - Cells, Cultured

KW - Diethylnitrosamine

KW - Down-Regulation

KW - Hepatic Stellate Cells

KW - Liver Cirrhosis

KW - Liver Neoplasms, Experimental

KW - Male

KW - Mice

KW - Mice, Inbred C57BL

U2 - 10.1136/gut.2010.209551

DO - 10.1136/gut.2010.209551

M3 - SCORING: Journal article

C2 - 21278145

VL - 60

SP - 1260

EP - 1268

JO - GUT

JF - GUT

SN - 0017-5749

IS - 9

ER -