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논문분류	춘계학술대회 초록집
제목	cMet agonistic antibody attenuates renal fibrosis in obstructive nephropathy
저자	Yong Chul Kim1, Jung Nam An2, Jin Hyuk Kim2, Young-Wook Choi2, Chun Soo Lim2, Yon Su Kim1, Seung Hee Yang3, Jung Pyo Lee2
출판정보	2018; 2018(1):
키워드	cMet agonistic antibody \| renal fibrosis \| proximal tubular cells \| unilateral ureteral obstruction
초록	Objectives: Hepatocyte growth factor (HGF) and its receptor, cMet, activate biological pathways necessary for repair and regeneration following kidney injury. The Met receptor is expressed in multiple cell types within the kidney, each of which is capable of regulating fibrotic responses. Since HGF is a quite unstable molecule in its biologically active form, we asked whether a monoclonal antibody (Ab) that displays receptor full agonist activity could protect kidney from fibrosis. Methods: We tried to determine whether cMet agonistic Ab might reduce fibrosis, the final common pathway for chronic kidney diseases. We primary cultured human proximal tubular epithelial cells (PTECs) for in vitro study and a mouse model of renal fibrosis disease induced by unilateral ureteral obstruction (UUO) was introduced. Results: In kidney biopsy specimens of CKD patients, cMet immunohistochemistry staining showed remarkable increase than patients with normal renal functions. cMet Ab treatment significantly increased phospho-cMet expression and abrogated protein expressions of fibrosis markers such as fibronectin, collagen IV, αSMA and also Bax2 which is a marker of apoptosis triggered by recombinant TGF-β1 in PTECs. In a wound healing scratch assay, PTECs treated with cMet Ab progressed into the wound area more rapidly inducing wound healing than untreated cells. Remarkably, injections of cMet Ab significantly prevented renal fibrosis in the obstructed kidneys quantified by Masson Trichrome staining. Consistently, cMet Ab decreased the expression of fibrosis markers such as, collagen 1 and αSMA, and E-cadherin which is a cell-to-cell adhesion molecule was recovered. Conclusions: cMet-mediated signaling may have a considerable role in the renal fibrosis. And cMet agonistic Ab may thus be a valuable substitute for HGF, being more easily available in a biologically active, stabilized, and purified form.
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