The Association Between Mechanosensitive Ion Channel Piezo2 Expression and Fibrogenesis in Hypertensive Diabetic Kidney Disease
- Diabetic Kidney Disease: Basic - II
November 04, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Diabetic Kidney Disease
- 701 Diabetic Kidney Disease: Basic
- Oba, Rina, Department of Anatomy, Kyorin University School of Medicine, Tokyo, Japan
- Kanzaki, Go, Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
- Yokoo, Takashi, Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
- Nagase, Miki, Department of Anatomy, Kyorin University School of Medicine, Tokyo, Japan
Diabetic kidney disease (DKD) is the leading cause of end-stage kidney disease, and mechanical forces such as glomerular hyperfiltration are crucial in the pathogenesis and progression of DKD. We previously reported Piezo2 expression in mouse kidneys and its alteration by dehydration and hypertension, however, the role of Piezo2 in DKD is still unclear. We aimed to elucidate Piezo2 expression and regulation in mouse models of DKD.
We used two types of DKD models (high fat diet (HFD) and streptozotocin (STZ)-treated C57BL/6J mouse, and high salt (HS)-treated type 2 diabetic KK-Ay mouse) and non-diabetic control C57BL/6J mice. Blood samples and kidneys were collected at 29 weeks of age in HFD+STZ mice and 19 weeks of age in KK-Ay+HS mice. We examined blood and urine analyses, histopathologic and immunohistochemical evaluations of kidneys, and gene expression analysis. The localization of Piezo2 expression was identified using in situ hybridization method.
Both DKD models exhibited significant obesity, hyperglycemia, albuminuria, glomerular hypertrophy, mesangial expansion, infiltration of macrophages, and tubular vacuolization compared to control mice. These findings were more severe in KK-Ay+HS mice than in HFD+STZ mice. KK-Ay+HS mice showed hypertension. Fibronectin protein expression was significantly upregulated in the glomerular areas of KK-Ay+HS mice kidneys. In addition, there were no significant differences in interstitial fibrosis between HFD+STZ mice and control mice, whereas severe interstitial fibrosis was observed in KK-Ay+HS mice kidneys. In situ hybridization studies showed no significant difference in Piezo2 expression between HFD+STZ mice and control mice, but Piezo2 expression was increased and localized in the glomerular and interstitial regions in KKAy+HS mice. Real-time RT-PCR showed that Piezo2 and Fn1 mRNA were increased in KKAy+HS mice compared with control mice. Furthermore, Piezo2 expression was strongly correlated with Fn1 expression (ρ=0.92, P<0.001).
Our findings suggest that Piezo2 expression is upregulated in glomerular and interstitial regions in the advanced stage of DKD with increased glomerular mechanical stress, and Piezo2 is associated with kidney fibrosis.