Endothelial autophagy deficiency induces interleukin 6-dependent endothelial mesenchymal transition and organ fibrosis
Description: Inhibition of autophagy, either by a specific inhibitor or siRNA for Atg5, in human microvascular endothelial cells (HMVECs) induced EndMT. The IL-6 level was significantly higher in Atg5 siRNA-transfected HMVEC culture medium compared with the control HMVEC culture medium, and neutralization of IL-6 by a specific antibody completely inhibited EndMT in Atg5 siRNA transfected HMVECs. Similar to the in vitro data, endothelial-specific Atg5 knockout mice (Atg5endo; Cdh5-Cre Atg5flox/flox mice) displayed both EndMT-associated kidney and heart fibrosis when compared to littermate controls. The plasma level of IL-6 was higher in Atg5endo mice compared to that of control mice, and fibrosis was accelerated in Atg5endo mice treated with HFD; neutralization of IL-6 by a specific antibody inhibited EndMT and fibrosis in HFD-fed Atg5endo mice associated with the amelioration of metabolic defects.
Amount: ¥3,510,000
Funding type: research
Funder scheme: Grant-in-Aid for Challenging Exploratory Research
Start date: 2016-04-01
End date: 2019-03-31
Investigator: Daisuke KOYA
Institution: Kanazawa Medical University
Funded outputs count: 14
Funder award ID: 16K15472
OpenAlex ID: G5602436050