| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| 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.
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