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  • Title: Activation of Wnt5a-Ror2 signaling associated with epithelial-to-mesenchymal transition of tubular epithelial cells during renal fibrosis.
    Author: Li X, Yamagata K, Nishita M, Endo M, Arfian N, Rikitake Y, Emoto N, Hirata K, Tanaka Y, Minami Y.
    Journal: Genes Cells; 2013 Jul; 18(7):608-19. PubMed ID: 23755735.
    Abstract:
    Activation of Wnt5a-Ror2 signaling has been shown to be associated with epithelial-to-mesenchymal transition (EMT) of epidermoid carcinoma cells via induction of matrix metalloproteinase-2 (MMP-2). Because EMT has also been implicated in the progression of tissue fibrosis, we examined the possible association of Wnt5a-Ror2 signaling with renal fibrosis. Here, we show that expression of Wnt5a and Ror2 is induced in a damaged mouse kidney after unilateral ureteral obstruction (UUO) treatment. Immunofluorescent analysis showed that Ror2 expression is clearly induced in tubular epithelial cells during renal fibrosis, and these Ror2-expressing cells also express Snail and vimentin, markers of mesenchymal cells, suggesting that Ror2 might be induced in epithelial cells undergoing EMT. We also found that MMP-2 expression is induced at Ror2-positive epithelium adjacent to significantly disrupted tubular basement membrane (TBM). Interestingly, reduced expression of MMP-2 is detected at epithelium in damaged kidneys from Ror2(+/-) mice compared with those from wild-type Ror2(+/+) mice. Importantly, extents of TBM disruption are apparently reduced in damaged kidneys from Ror2(+/-) mice compared with those from wild-type mice. Collectively, these findings indicate that activation of Wnt5a-Ror2 signaling in epithelial cells undergoing EMT may play an important role in disrupting TBM via MMP-2 induction during renal fibrosis.
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