title: Activation of Wnt5a-Ror2 signaling associated with epithelial-to-mesenchymal transition of tubular epithelial cells during renal fibrosis.
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.
authors.affiliation: Division of Cell Physiology, Department of Physiology and Cell Biology, Graduate School of Medicine, Kobe University, 7-5-1, Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.forename: Kaoru
authors.initials: K
authors.lastname: Yamagata
authors.forename: Michiru
authors.initials: M
authors.lastname: Nishita
authors.forename: Mitsuharu
authors.initials: M
authors.lastname: Endo
authors.forename: Nur
authors.initials: N
authors.lastname: Arfian
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Rikitake
authors.forename: Noriaki
authors.initials: N
authors.lastname: Emoto
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Hirata
authors.forename: Yoshiya
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Minami
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition; D005355:Fibrosis / Q000378:metabolism* / Q000473:pathology; D007674:Kidney Diseases / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D057050:Receptor Tyrosine Kinase-like Orphan Receptors / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism*; D000071818:Wnt-5a Protein
chemical_list: D051153:Wnt Proteins; D000071818:Wnt-5a Protein; C438615:Wnt5a protein, mouse; D057050:Receptor Tyrosine Kinase-like Orphan Receptors; C477010:Ror2 protein, mouse