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2016 Fiscal Year Final Research Report

Involvement of LPA1-MRTF-SRF in renal fibrosis

Research Project

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Project/Area Number 26461218
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Kidney internal medicine
Research InstitutionKanazawa University

Principal Investigator

SAKAI NORIHIKO  金沢大学, 附属病院, 助教 (60377421)

Co-Investigator(Renkei-kenkyūsha) WADA TAKASHI  金沢大学, 医学系, 教授 (40334784)
Research Collaborator Tager Andrew M.  
Project Period (FY) 2014-04-01 – 2017-03-31
Keywords線維化 / 腎臓
Outline of Final Research Achievements

Fibrosis is charactereized by the expansion of the fibroblast pool, but the mechanisms driving it remain to be fully clarified. We found that lysophosphatidic acid (LPA) and its receptor (LPA1) signaling drives fibroblast proliferation and activation during the development of renal fibrosis by inducing connective tissue growth factor (CTGF). Unilateral ureteral obstruction (UUO)-induced increases in renal collagen were significantly attenuated in LPA1-deficient mice (LPA1-/-) as compared to LPA1-sufficient mice (LPA+/+), as was the accumulations of fibroblasts. CTGF was detected mainly in tubular epithelial cells, and its levels were suppressed in LPA1-/-. LPA-LPA1 signaling directly induced CTGF expression by primary proximal tubular epithelial cells (PTECs). PTEC-derived CTGF mediated renal fibroblast proliferation and myofibroblast differentiation. These results suggest that targeting LPA-LPA1 signaling could be a therapeutic strategy for renal fibrosis.

Free Research Field

腎臓内科

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Published: 2018-03-22  

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