肾
纤维化
肾脏疾病
急性肾损伤
医学
上皮-间质转换
内科学
癌症研究
内分泌学
SMAD公司
转化生长因子
癌症
转移
作者
Lilin Li,Jeonghwan Lee,Ara Cho,Jin‐Hyuk Kim,William Ju,Jung Nam An,Jeong Hwan Park,Shi Mao Zhu,Jung-Hun Lee,Seung Shin Yu,Chun Soo Lim,Yon Su Kim,Yon Su Kim,Seung Hee Yang,Jung Pyo Lee
出处
期刊:Clinical Science
[Portland Press]
日期:2021-06-01
卷期号:135 (11): 1427-1444
被引量:3
摘要
We aimed to investigate the role of cMet agonistic antibody (cMet Ab) in preventing kidney fibrosis during acute kidney injury (AKI) to chronic kidney disease (CKD) transition. Additionally, we explored the effect of cMet Ab on TGF-β1/Smad pathway during the pathogenesis of kidney fibrosis. A unilateral ischemia-reperfusion injury (UIRI) mouse model was established to induce AKI-to-CKD transition. Furthermore, we incubated human proximal tubular epithelial cells (hPTECs) under hypoxic conditions as in vitro model of kidney fibrosis. We analyzed the soluble plasma cMet level in patients with AKI requiring dialysis. Patients who did not recover kidney function and progressed to CKD presented a higher increase in the cMet level. The kidneys of mice treated with cMet Ab showed fewer contractions and weighed more than the controls. The mice in the cMet Ab-treated group showed reduced fibrosis and significantly decreased expression of fibronectin and α-smooth muscle actin. cMet Ab treatment decreased inflammatory markers (MCP-1, TNF-α, and IL-1β) expression, reduced Smurf1 and Smad2/3 level, and increased Smad7 expressions. cMet Ab treatment increased cMet expression and reduced the hypoxia-induced increase in collagen-1 and ICAM-1 expression, thereby reducing apoptosis in the in vitro cell model. After cMet Ab treatment, hypoxia-induced expression of Smurf1, Smad2/3, and TGF-β1 was reduced, and suppressed Smad7 was activated. Down-regulation of Smurf1 resulted in suppression of hypoxia-induced fibronectin expression, whereas treatment with cMet Ab showed synergistic effects. cMet Ab can successfully prevent fibrosis response in UIRI models of kidney fibrosis by decreasing inflammatory response and inhibiting the TGF-β1/Smad pathway.
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