Abstract: TH-PO225
NCOA1 Modulates Glomerulosclerosis in Diabetic Kidney Disease Through Regulating ITGA5
Session Information
- Diabetic Kidney Disease: Basic - I
November 03, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
Abstract Time: 10:00 AM - 12:00 PM
Category: Diabetic Kidney Disease
- 601 Diabetic Kidney Disease: Basic
Authors
- Gai, Lili, Huazhong University of Science and Technology, Wuhan, Hubei, China
- Zhang, Chun, Huazhong University of Science and Technology, Wuhan, Hubei, China
Background
Nuclear receptor coactivator 1 (NCOA1) is a member of NCOA family, which coactivate and potentiate the expression of target genes, regulating various biological events such as cell proliferation and fibrosis. Recent findings revealed a potential role of NCOA1 in metabolic related diseases and tissue fibrosis. However, its role in glomerulosclerosis of diabetic kidney disease (DKD) remains unclear. Previous data reported NCOA1 could directly enhance integrin alpha 5 (ITGA5) expression and thus promoting ITGA5-mediated biological events. ITGA5 is a cell adhesion protein, which also plays an indispensable role in various tissue fibrosis. Therefore, our study aims to explore whether NCOA1 can be involved in glomerulosclerosis in diabetic kidney disease by regulating ITGA5.
Methods
1. The model of DKD was established by intraperitoneally injection of 150mg/kg streptozotocin in 8-week-old mice.
2. The expression of NCOA1 in renal cortex of DKD mice and glomerular mesangial cells (GMCs) treated by high glucose (HG) were detected by quantitative real-time polymerase chain reaction (qRT-PCR), westernblot (WB) and immunofluorescence. The expression of Fibronectin and Collagen IV was detected by WB after HG treated GMCs were transfected with NCOA1 overexpression plasmid.
3. The expression of ITGA5 in vivo and vitro was detected by qRT-PCR, WB and immunofluorescence in DKD, and the expression of Fibronectin and Collagen IV was detected by WB after HG treated GMCs were transfected with ITGA5 siRNA.
4. The expression of ITGA5 was detected by WB after HG treated GMCs were transfected with NCOA1 overexpression plasmid.
Results
1. The expression of NCOA1 was significantly downregulated in DKD mice and HG-treated GMCs, while overexpression of NCOA1 by plasmid could attenuate HG-induced extracellular matrix (ECM) accumulation in GMCs.
2. The expression of ITGA5 was significantly upregulated in vivo and in vitro of DKD, while knocking down ITGA5 by siRNA could attenuate HG-induced ECM accumulation in GMCs.
3. The activation of ITGA5 induced by HG was obviously attenuated by NCOA1 overexpression in GMCs.
Conclusion
NCOA1 might be involved in glomerulosclerosis of DKD by regulating the expression of ITGA5.