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Liver knockout YAP gene improved insulin resistance-induced hepatic fibrosis
- Source :
- Journal of Endocrinology. 249:149-161
- Publication Year :
- 2021
- Publisher :
- Bioscientifica, 2021.
-
Abstract
- Yes-associated protein (YAP), as a co-activator of transcription factors, is a downstream protein in the Hippo signaling pathway with important functions in cell proliferation, apoptosis, invasion and migration. YAP also plays a key role in the development of CCl4-induced liver fibrosis. However, the mechanism of YAP during hepatic fibrosis progression and reversion is still unclear. Mild liver fibrosis was developed after 4 months of high-fat diet (HFD) stimulation, and we found that the YAP signaling pathway was activated. Here, we aim to reveal whether specific knockout of Yap gene in the liver can improve liver fibrosis induced by insulin resistance (IR) stimulated by HFD, and further explain its specific mechanism. We found that liver-specific Yap gene knockout improved IR-induced liver fibrosis and liver dysfunction, and this mechanism is related to the inhibition of the insulin signal pathway at the FoxO1 level. These findings provide a new insight, and Yap is expected to be a new target to reverse the early stage of liver fibrosis induced by IR.
- Subjects :
- Liver Cirrhosis
0301 basic medicine
medicine.medical_specialty
Endocrinology, Diabetes and Metabolism
medicine.medical_treatment
030209 endocrinology & metabolism
FOXO1
CCL4
Diet, High-Fat
Mice
03 medical and health sciences
0302 clinical medicine
Endocrinology
Insulin resistance
Internal medicine
Animals
Humans
Medicine
Transcription factor
Adaptor Proteins, Signal Transducing
Mice, Knockout
Hippo signaling pathway
Forkhead Box Protein O1
business.industry
Insulin
YAP-Signaling Proteins
Glucose Tolerance Test
medicine.disease
Glucose
HEK293 Cells
030104 developmental biology
Gene Expression Regulation
Liver
Hepatocytes
Cancer research
Insulin Resistance
Signal transduction
business
Hepatic fibrosis
Signal Transduction
Subjects
Details
- ISSN :
- 14796805 and 00220795
- Volume :
- 249
- Database :
- OpenAIRE
- Journal :
- Journal of Endocrinology
- Accession number :
- edsair.doi.dedup.....b971ec3ed8339a688e015049e8d08364