Abstract: PO0931
Overexpression of ACE in Macrophages Accelerates Diabetic Kidney Disease
Session Information
- Diabetic Kidney Disease: New Pathways and Therapies
October 22, 2020 | Location: On-Demand
Abstract Time: 10:00 AM - 12:00 PM
Category: Diabetic Kidney Disease
- 601 Diabetic Kidney Disease: Basic
Authors
- Tomita, Keigo, Department of Medicine and Clinical Science, Graduate School of Medical Science, Fukuoka, Fukuoka, Japan
- Eriguchi, Masahiro, Department of Nephrology, Nara Medical University, Kashihara, Nara, Japan
- Torisu, Kumiko, Department of Medicine and Clinical Science, Graduate School of Medical Science, Fukuoka, Fukuoka, Japan
- Giani, Jorge F., Cedars-Sinai Medical Center, Departments of Biomedical Sciences, Los Angeles, California, United States
- Bernstein, Kenneth E., Cedars-Sinai Medical Center, Departments of Biomedical Sciences, Los Angeles, California, United States
- Tsuruya, Kazuhiko, Department of Nephrology, Nara Medical University, Kashihara, Nara, Japan
- Nakano, Toshiaki, Department of Medicine and Clinical Science, Graduate School of Medical Science, Fukuoka, Fukuoka, Japan
- Kitazono, Takanari, Department of Medicine and Clinical Science, Graduate School of Medical Science, Fukuoka, Fukuoka, Japan
Background
We previously reported that renal tubular angiotensin-converting enzyme (ACE) is mainly involved in the pathological progression in diabetic kidney disease (DKD). Although ACE in macrophages has been shown to be important in controlling inflammation, the expression and function of ACE in macrophages in DKD are still unknown.
Methods
Diabetes was induced by five consecutive daily intraperitoneal injections of streptozotocin (55 mg/kg) using C57Bl6/J male mice. Primary peritoneal macrophages were harvested after intraperitoneal injection with 2 mL of 4% thioglycolate solution into mice. Mouse-ACE overexpressing plasmid was electroporated into Raw 264.7 to evaluate cytokine release and migration ability. ACE 10/10 mice was deficient of ACE in the whole body but overexpressed only in monocytes/macrophages. We induced diabetes in ACE 10/10 and wild-type mice and analyzed albuminuria or pathological changes of kidney after six months of diabetes.
Results
ACE mRNA was increased in peripheral blood monocytes and peritoneal macrophages from diabetic mice. LPS-induced release of IL-6 and nitric oxide was increased in macrophages overexpressing ACE. The migration ability of macrophages overexpressing ACE was higher than that of control vector-expressing cells. In diabetic ACE 10/10 mice, glomerular hypertrophy and glomerular hyperfiltration were not evident as in diabetic wild-type mice. Although ACE 10/10 mice lacks ACE in vascular endothelial cells and tubular cells, mesangial expansion and interstitial fibrosis in the kidney, and albuminuria from diabetic ACE 10/10 mice were similar to those from diabetic wild-type mice.
Conclusion
In diabetes, the expression of ACE in macrophage is enhanced. As a result, dysregulation of macrophage function occurred, and it may be involved in the development of diabetic kidney disease.