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Renoprotective effects of a novel cMet agonistic antibody on kidney fibrosis.
Kim, Yong Chul; Lee, Junghun; An, Jung Nam; Kim, Jin Hyuk; Choi, Young-Wook; Li, Lilin; Kwon, Sang Ho; Lee, Mi-Young; Lee, Boeun; Jeong, Jae-Gyun; Yu, Seung-Shin; Lim, Chun Soo; Kim, Yon Su; Kim, Sunyoung; Yang, Seung Hee; Lee, Jung Pyo.
Afiliación
  • Kim YC; Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.
  • Lee J; R&D Center for Innovative Medicines, Helixmith Co., Ltd., Seoul, Korea.
  • An JN; Department of Internal Medicine, Seoul National University Boramae Medical Center, Seoul, Korea.
  • Kim JH; Department of Internal Medicine, Seoul National University Boramae Medical Center, Seoul, Korea.
  • Choi YW; Department of Internal Medicine, Seoul National University Boramae Medical Center, Seoul, Korea.
  • Li L; Department of Internal Medicine, Seoul National University Boramae Medical Center, Seoul, Korea.
  • Kwon SH; Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
  • Lee MY; R&D Center for Innovative Medicines, Helixmith Co., Ltd., Seoul, Korea.
  • Lee B; R&D Center for Innovative Medicines, Helixmith Co., Ltd., Seoul, Korea.
  • Jeong JG; R&D Center for Innovative Medicines, Helixmith Co., Ltd., Seoul, Korea.
  • Yu SS; R&D Center for Innovative Medicines, Helixmith Co., Ltd., Seoul, Korea.
  • Lim CS; R&D Center for Innovative Medicines, Helixmith Co., Ltd., Seoul, Korea.
  • Kim YS; Department of Internal Medicine, Seoul National University Boramae Medical Center, Seoul, Korea.
  • Kim S; Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
  • Yang SH; Department of Medical Science, Seoul National University College of Medicine, Seoul, Korea.
  • Lee JP; Kidney Research Institute, Seoul National University College of Medicine, Seoul, Korea.
Sci Rep ; 9(1): 13495, 2019 09 17.
Article en En | MEDLINE | ID: mdl-31530851
Hepatocyte growth factor (HGF) and its receptor, cMet, activate biological pathways necessary for repair and regeneration following kidney injury. Because HGF is a highly unstable molecule in its biologically active form, we asked whether a monoclonal antibody (Ab) that displays full agonist activity at the receptor could protect the kidney from fibrosis. We attempted to determine whether the cMet agonistic Ab might reduce fibrosis, the final common pathway for chronic kidney diseases (CKD). A mouse model of kidney fibrosis disease induced by unilateral ureteral obstruction was introduced and subsequently validated with primary cultured human proximal tubular epithelial cells (PTECs). In kidney biopsy specimens from patients with CKD, cMet immunohistochemistry staining showed a remarkable increase compared with patients with normal renal functions. cMet Ab treatment significantly increased the levels of phospho-cMet and abrogated the protein expression of fibrosis markers such as fibronectin, collagen 1, and αSMA as well as Bax2, which is a marker of apoptosis triggered by recombinant TGF-ß1 in PTECs. Remarkably, injections of cMet Ab significantly prevented kidney fibrosis in obstructed kidneys as quantified by Masson trichrome staining. Consistent with these data, cMet Ab treatment decreased the expression of fibrosis markers, such as collagen1 and αSMA, whereas the expression of E-cadherin, which is a cell-cell adhesion molecule, was restored. In conclusion, cMet-mediated signaling may play a considerable role in kidney fibrosis. Additionally, the cMet agonistic Ab may be a valuable substitute for HGF because it is more easily available in a biologically active, stable, and purified form.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas Proto-Oncogénicas c-met / Sustancias Protectoras / Insuficiencia Renal Crónica / Anticuerpos Monoclonales Tipo de estudio: Etiology_studies / Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Sci Rep Año: 2019 Tipo del documento: Article Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas Proto-Oncogénicas c-met / Sustancias Protectoras / Insuficiencia Renal Crónica / Anticuerpos Monoclonales Tipo de estudio: Etiology_studies / Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Sci Rep Año: 2019 Tipo del documento: Article Pais de publicación: Reino Unido