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Increased Levels of Phosphorylated ERK Induce CTGF Expression in Autophagy-Deficient Mouse Hepatocytes

Autophagy performs essential cell functions in the liver through an intracellular lysosomal degradation process. Several studies have reported that autophagy deficiency can lead to liver injury, including hepatic fibrosis; however, the mechanisms underlying the relationship between autophagy deficie...

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Autores principales: Seo, Hye-Young, Lee, So-Hee, Han, Eugene, Hwang, Jae Seok, Kim, Mi Kyung, Jang, Byoung Kuk
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9454551/
https://www.ncbi.nlm.nih.gov/pubmed/36078110
http://dx.doi.org/10.3390/cells11172704
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author Seo, Hye-Young
Lee, So-Hee
Han, Eugene
Hwang, Jae Seok
Kim, Mi Kyung
Jang, Byoung Kuk
author_facet Seo, Hye-Young
Lee, So-Hee
Han, Eugene
Hwang, Jae Seok
Kim, Mi Kyung
Jang, Byoung Kuk
author_sort Seo, Hye-Young
collection PubMed
description Autophagy performs essential cell functions in the liver through an intracellular lysosomal degradation process. Several studies have reported that autophagy deficiency can lead to liver injury, including hepatic fibrosis; however, the mechanisms underlying the relationship between autophagy deficiency and liver pathology are unclear. In this study, we examined the expression levels of fibrosis-associated genes in hepatocyte-specific ATG7-deficient mice. The expression levels of the connective tissue growth factor (CTGF) and phosphorylated ERK (phospho-ERK) proteins were increased significantly in primary hepatocytes isolated from hepatocyte-specific ATG7-deficient mice compared to those isolated from control mice. In addition, the inhibition of autophagy in cultured mammalian hepatic AML12 and LX2 cells increased CTGF and phospho-ERK protein levels without altering CTGF mRNA expression. In addition, the autophagy deficiency-mediated enhancement of CTGF expression was attenuated when ERK was inhibited. Overall, these results suggest that the inhibition of autophagy in hepatocytes increases phospho-ERK expression, which in turn increases the expression of CTGF, a biomarker of fibrosis.
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spelling pubmed-94545512022-09-09 Increased Levels of Phosphorylated ERK Induce CTGF Expression in Autophagy-Deficient Mouse Hepatocytes Seo, Hye-Young Lee, So-Hee Han, Eugene Hwang, Jae Seok Kim, Mi Kyung Jang, Byoung Kuk Cells Article Autophagy performs essential cell functions in the liver through an intracellular lysosomal degradation process. Several studies have reported that autophagy deficiency can lead to liver injury, including hepatic fibrosis; however, the mechanisms underlying the relationship between autophagy deficiency and liver pathology are unclear. In this study, we examined the expression levels of fibrosis-associated genes in hepatocyte-specific ATG7-deficient mice. The expression levels of the connective tissue growth factor (CTGF) and phosphorylated ERK (phospho-ERK) proteins were increased significantly in primary hepatocytes isolated from hepatocyte-specific ATG7-deficient mice compared to those isolated from control mice. In addition, the inhibition of autophagy in cultured mammalian hepatic AML12 and LX2 cells increased CTGF and phospho-ERK protein levels without altering CTGF mRNA expression. In addition, the autophagy deficiency-mediated enhancement of CTGF expression was attenuated when ERK was inhibited. Overall, these results suggest that the inhibition of autophagy in hepatocytes increases phospho-ERK expression, which in turn increases the expression of CTGF, a biomarker of fibrosis. MDPI 2022-08-30 /pmc/articles/PMC9454551/ /pubmed/36078110 http://dx.doi.org/10.3390/cells11172704 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Seo, Hye-Young
Lee, So-Hee
Han, Eugene
Hwang, Jae Seok
Kim, Mi Kyung
Jang, Byoung Kuk
Increased Levels of Phosphorylated ERK Induce CTGF Expression in Autophagy-Deficient Mouse Hepatocytes
title Increased Levels of Phosphorylated ERK Induce CTGF Expression in Autophagy-Deficient Mouse Hepatocytes
title_full Increased Levels of Phosphorylated ERK Induce CTGF Expression in Autophagy-Deficient Mouse Hepatocytes
title_fullStr Increased Levels of Phosphorylated ERK Induce CTGF Expression in Autophagy-Deficient Mouse Hepatocytes
title_full_unstemmed Increased Levels of Phosphorylated ERK Induce CTGF Expression in Autophagy-Deficient Mouse Hepatocytes
title_short Increased Levels of Phosphorylated ERK Induce CTGF Expression in Autophagy-Deficient Mouse Hepatocytes
title_sort increased levels of phosphorylated erk induce ctgf expression in autophagy-deficient mouse hepatocytes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9454551/
https://www.ncbi.nlm.nih.gov/pubmed/36078110
http://dx.doi.org/10.3390/cells11172704
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