Abstract: TH-PO500
Agonistic cMet Antibody Prevents Kidney Fibrosis in Acute Kidney Disease Mice Model
Session Information
- CKD: Mechanisms - I
November 07, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 2103 CKD (Non-Dialysis): Mechanisms
Authors
- Lee, Jeonghwan, Hallym University Hangang Sacred Heart Hospital, Seoul, Korea (the Republic of)
- Li, Lilin, Seoul National University College of Medicine, Boramae Medical Center, Seoul, Korea (the Republic of)
- Lee, Jung Pyo, Seoul National University Boramae Medical Center, Seoul, Korea (the Republic of)
Background
HGF/cMet signaling pathway plays important roles in kidney development and maintenance of normal adult kidney structure, and cMet activation is expected to prevent kidney fibrosis. We aimed to investigate whether treatment with agnostic cMet antibody can prevent kidney fibrosis in the acute kidney disease mice model.
Methods
Unilateral ischemic-reperfusion injury at left kidney was introduced in 7-week-old male C57BL/6 mice (n = 14) and raised for up to 28 days to induce acute kidney disease model. Agnostic cMet antibody (20 mg/kg) was injected via tail vein at a schedule of day -1, 0, 1, 3, and twice weekly thereafter in the treatment group (n = 7). Vehicle (saline) was injected via tail vein at the same schedule in the control group (n = 7).
Results
Kidney weight (left) per total body weight was significantly higher in the treatment group (0.63 ± 0.21% vs. 0.43 ± 0.22%, P = 0.022). In the histopathologic specimen of Masson's trichrome stain, areas of kidney interstitial fibrosis attenuated in the treatment group. In the western-blot analysis, protein abundance of α-smooth muscle actin (22.5% of control, P = 0.03), fibronectin (16.4% of control, P = 0.03), TGF-β (33.3% of control, P = 0.05), total (6.6% of control, P = 0.03) and phospho-smad2/3 (10.1% of control, P = 0.03) decreased significantly, and protein abundance of e-cadherin increased (912.4% of control, P = 0.03) significantly in the treatment group. In the real-time PCR analysis, mRNA expression of α-smooth muscle actin (11.5% of control, P = 0.006), collagen 1 (11.6% of control, P = 0.01), fibronectin (11.2% of control, P = 0.01), TGF-β (21.3% of control, P = 0.01) decreased significantly in the treatment group.
Conclusion
Agonistic cMet antibody attenuates kidney fibrosis in the mice unilateral ischemic reperfusion induced acute kidney disease model, and TGF-β and smad2/3 pathway involved in the kidney fibrosis are effectively suppressed in the treatment of agonistic cMet antibody.
Western Blot Results after Agonistic cMet Antibody Treatment