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Title: Insulin-induced CARM1 upregulation facilitates hepatocyte proliferation

Abstract

Previously, we reported that CARM1 undergoes ubiquitination-dependent degradation in renal podocytes. It was also reported that CARM1 is necessary for fasting-induced hepatic gluconeogenesis. Based on these reports, we hypothesized that treatment with insulin, a hormone typically present under the ‘fed’ condition, would inhibit gluconeogenesis via CARM1 degradation. HepG2 cells, AML-12 cells, and rat primary hepatocytes were treated with insulin to confirm CARM1 downregulation. Surprisingly, insulin treatment increased CARM1 expression in all cell types examined. Furthermore, treatment with insulin increased histone 3 methylation at arginine 17 and 26 in HepG2 cells. To elucidate the role of insulin-induced CARM1 upregulation, the HA-CARM1 plasmid was transfected into HepG2 cells. CARM1 overexpression did not increase the expression of lipogenic proteins generally increased by insulin signaling. Moreover, CARM1 knockdown did not influence insulin sensitivity. Insulin is known to facilitate hepatic proliferation. Like insulin, CARM1 overexpression increased CDK2 and CDK4 expression. In addition, CARM1 knockdown reduced the number of insulin-induced G2/M phase cells. Moreover, GFP-CARM1 overexpression increased the number of G2/M phase cells. Based on these results, we concluded that insulin-induced CARM1 upregulation facilitates hepatocyte proliferation. These observations indicate that CARM1 plays an important role in liver pathophysiology. - Highlights: • Insulin treatment increases CARM1 expressionmore » in hepatocytes. • CARM1 overexpression does not increase the expression of lipogenic proteins. • CARM1 knockdown does not influence insulin sensitivity. • Insulin-induced CARM1 upregulation facilitates hepatocyte proliferation.« less

Authors:
; ; ;  [1]; ; ;  [2];  [3];  [1]
  1. College of Veterinary Medicine, Chonnam National University, Gwangju 500-757 (Korea, Republic of)
  2. Jeollanamdo Forest Resources Research Institute, Naju 520-833 (Korea, Republic of)
  3. College of Veterinary Medicine, Seoul National University, Seoul 151-741 (Korea, Republic of)
Publication Date:
OSTI Identifier:
22462076
Resource Type:
Journal Article
Journal Name:
Biochemical and Biophysical Research Communications
Additional Journal Information:
Journal Volume: 461; Journal Issue: 3; Other Information: Copyright (c) 2015 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0006-291X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ARGININE; CELL PROLIFERATION; FASTING; INSULIN; KIDNEYS; LIVER; LIVER CELLS; METHYLATION; RATS; SENSITIVITY; SIGNALS

Citation Formats

Yeom, Chul-gon, Kim, Dong-il, Park, Min-jung, Choi, Joo-hee, Jeong, Jieun, Wi, Anjin, Park, Whoashig, Han, Ho-jae, and Park, Soo-hyun. Insulin-induced CARM1 upregulation facilitates hepatocyte proliferation. United States: N. p., 2015. Web. doi:10.1016/J.BBRC.2015.04.099.
Yeom, Chul-gon, Kim, Dong-il, Park, Min-jung, Choi, Joo-hee, Jeong, Jieun, Wi, Anjin, Park, Whoashig, Han, Ho-jae, & Park, Soo-hyun. Insulin-induced CARM1 upregulation facilitates hepatocyte proliferation. United States. doi:10.1016/J.BBRC.2015.04.099.
Yeom, Chul-gon, Kim, Dong-il, Park, Min-jung, Choi, Joo-hee, Jeong, Jieun, Wi, Anjin, Park, Whoashig, Han, Ho-jae, and Park, Soo-hyun. Fri . "Insulin-induced CARM1 upregulation facilitates hepatocyte proliferation". United States. doi:10.1016/J.BBRC.2015.04.099.
@article{osti_22462076,
title = {Insulin-induced CARM1 upregulation facilitates hepatocyte proliferation},
author = {Yeom, Chul-gon and Kim, Dong-il and Park, Min-jung and Choi, Joo-hee and Jeong, Jieun and Wi, Anjin and Park, Whoashig and Han, Ho-jae and Park, Soo-hyun},
abstractNote = {Previously, we reported that CARM1 undergoes ubiquitination-dependent degradation in renal podocytes. It was also reported that CARM1 is necessary for fasting-induced hepatic gluconeogenesis. Based on these reports, we hypothesized that treatment with insulin, a hormone typically present under the ‘fed’ condition, would inhibit gluconeogenesis via CARM1 degradation. HepG2 cells, AML-12 cells, and rat primary hepatocytes were treated with insulin to confirm CARM1 downregulation. Surprisingly, insulin treatment increased CARM1 expression in all cell types examined. Furthermore, treatment with insulin increased histone 3 methylation at arginine 17 and 26 in HepG2 cells. To elucidate the role of insulin-induced CARM1 upregulation, the HA-CARM1 plasmid was transfected into HepG2 cells. CARM1 overexpression did not increase the expression of lipogenic proteins generally increased by insulin signaling. Moreover, CARM1 knockdown did not influence insulin sensitivity. Insulin is known to facilitate hepatic proliferation. Like insulin, CARM1 overexpression increased CDK2 and CDK4 expression. In addition, CARM1 knockdown reduced the number of insulin-induced G2/M phase cells. Moreover, GFP-CARM1 overexpression increased the number of G2/M phase cells. Based on these results, we concluded that insulin-induced CARM1 upregulation facilitates hepatocyte proliferation. These observations indicate that CARM1 plays an important role in liver pathophysiology. - Highlights: • Insulin treatment increases CARM1 expression in hepatocytes. • CARM1 overexpression does not increase the expression of lipogenic proteins. • CARM1 knockdown does not influence insulin sensitivity. • Insulin-induced CARM1 upregulation facilitates hepatocyte proliferation.},
doi = {10.1016/J.BBRC.2015.04.099},
journal = {Biochemical and Biophysical Research Communications},
issn = {0006-291X},
number = 3,
volume = 461,
place = {United States},
year = {2015},
month = {6}
}