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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Published inCells (Basel, Switzerland) Vol. 11; no. 17; p. 2704
Main Authors Seo, Hye-Young, Lee, So-Hee, Han, Eugene, Hwang, Jae Seok, Kim, Mi Kyung, Jang, Byoung Kuk
Format Journal Article
LanguageEnglish
Published Basel MDPI AG 30.08.2022
MDPI
Subjects
Analysis
Antibiotics
Antibodies
ATG7
Autophagy
Autophagy (Cytology)
Biotechnology
Collagen
Connective tissue
Connective tissue growth factor
Connective tissues
CTGF
ERK
Extracellular signal-regulated kinase
Extracellular signal-regulated kinases
Fibrosis
Gene expression
Growth factors
Health aspects
hepatocyte
Hepatocytes
Liver
Liver cells
Liver diseases
Lysosomes
Prevention
Risk factors
Software
South Korea
United States > US
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Summary: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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These authors contributed equally to this work.
ISSN:2073-4409
2073-4409
DOI:10.3390/cells11172704