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Pathology & Oncology Research

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14.08.2018 | Original Article

Chronic Hyperglycaemia Induced Alterations of Hepatic Stellate Cells Differ from the Effect of TGFB1, and Point toward Metabolic Stress

verfasst von: Katalin Kiss, Eszter Regős, Kristóf Rada, Gábor Firneisz, Kornélia Baghy, Ilona Kovalszky

Erschienen in: Pathology & Oncology Research | Ausgabe 1/2020

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Abstract

The deleterious effect of hyperglycemia on the biology of the liver is supported by clinical evidence. It can promote the development of fatty liver, liver fibrosis, even liver cancer as complication of diabetes mellitus. As liver fibrosis is the consequence of hepatic stellate cell (HSC) activation, the questions were addressed whether alterations induced by high glucose concentration are directly related to TGFB1 effect, or other mechanisms are activated. In order to obtain information on the response of HSC for high glucose, LX-2 cells (an immortalized human HSC cell lineage) were cultured in 15.3 mM glucose containing medium for 21 days. The effect of glucose was compared to that of TGFB1. Our data revealed that chronic exposure of high glucose concentration initiated profound alteration of LX-2 cells and the effect is different from those observed upon interaction with TGFB1. Whereas TGFB1 induced the production of extracellular matrix proteins, high glucose exposure resulted in decreased MMP2 activity, retardation of type I collagen in the endoplasmic reticulum, with decreased pS6 expression, pointing to development of endoplasmic stress and sequestration of p21^CIP1/WAF1 in the cytoplasm which can promote the proliferation of LX2 cells.

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Titel: Chronic Hyperglycaemia Induced Alterations of Hepatic Stellate Cells Differ from the Effect of TGFB1, and Point toward Metabolic Stress
verfasst von: Katalin Kiss
Eszter Regős
Kristóf Rada
Gábor Firneisz
Kornélia Baghy
Ilona Kovalszky
Publikationsdatum: 14.08.2018
Verlag: Springer Netherlands
Erschienen in: Pathology & Oncology Research / Ausgabe 1/2020
Print ISSN: 1219-4956
Elektronische ISSN: 1532-2807
DOI: https://doi.org/10.1007/s12253-018-0458-9

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