Format

Send to:

Choose Destination
See comment in PubMed Commons below
Biochim Biophys Acta. 2014 Sep;1842(9):1733-41. doi: 10.1016/j.bbadis.2014.06.022. Epub 2014 Jun 26.

Regulator of G protein signaling 2 (RGS2) deficiency accelerates the progression of kidney fibrosis.

Author information

  • 1Department of Anatomy, Cardiovascular Research Institute, BK21 Plus Biomedical Convergence Program, Kyungpook National University School of Medicine, Daegu 700-422, Republic of Korea.
  • 2Department of Molecular Medicine and Obesity-Mediated Disease Research Center, College of Medicine, Keimyung University, Daegu, 704-701, Republic of Korea.
  • 3Laboratory of Physiology and Signaling, College of Veterinary Medicine, Kyungpook National University, Daegu 702-701, Republic of Korea.
  • 4Department of Anatomy, Cardiovascular Research Institute, BK21 Plus Biomedical Convergence Program, Kyungpook National University School of Medicine, Daegu 700-422, Republic of Korea. Electronic address: kmpark@knu.ac.kr.

Abstract

The regulator of G protein signaling 2 (RGS2) is a potent negative regulator of Gq protein signals including the angiotensin II (AngII)/AngII receptor signal, which plays a critical role in the progression of fibrosis. However, the role of RGS2 on the progression of kidney fibrosis has not been assessed. Here, we investigated the role of RGS2 in kidney fibrosis induced by unilateral ureteral obstruction (UUO) in mice. UUO resulted in increased expression of RGS2 mRNA and protein in the kidney along with increases of AngII and its type 1 receptor (AT1R) signaling and fibrosis. Furthermore, UUO increased the levels of F4/80, Ly6G, myeloperoxidase, and CXCR4 in the kidneys. RGS2 deficiency significantly enhanced these changes in the kidney. RGS2 deletion in the bone marrow-derived cells by transplanting the bone marrow of RGS2 knock-out mice into wild type mice enhanced UUO-induced kidney fibrosis. Overexpression of RGS2 in HEK293 cells, a human embryonic kidney cell line, and RAW264.7 cells, a monocyte/macrophage line, inhibited the AngII-induced activation of ERK and increase of CXCR4 expression. These findings provide the first evidence that RGS2 negatively regulates the progression of kidney fibrosis following UUO, likely by suppressing fibrogenic and inflammatory responses through the inhibition of AngII/AT1R signaling.

Copyright © 2014 Elsevier B.V. All rights reserved.

KEYWORDS:

Angiotensin II; Fibrosis; GPCR signaling; Inflammation; RGS

PMID:
24973550
[PubMed - indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science
    Loading ...
    Write to the Help Desk