Kidney Week

Abstract: SA-PO524

Intrarenal Enhancement of Leucine-Rich α-2-Glycoprotein-1 in the Early Stage of Diabetic Nephropathy

Session Information

• Diabetic Kidney Disease: Basic - III
  November 09, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Diabetic Kidney Disease

• 601 Diabetic Kidney Disease: Basic

Authors

• Wakui, Hiromichi, Yokohama City University, Yokohama, Japan

Hiromichi Wakui,

• Kanaoka, Tomohiko, Yokohama City University, Yokohama, Japan

Tomohiko Kanaoka,

• Urate, Shingo, Yokohama City University Graduate School of Medicine, Yokohama-shi,Kanagawa-ken, Japan

Shingo Urate,

• Azushima, Kengo, Duke-NUS Medical School, Singapore, Singapore

Kengo Azushima,

• Yamada, Takayuki, Yokohama City University, Yokohama, Japan

Takayuki Yamada,

• Yamaji, Takahiro, Yokohama City University Graduate School of Medicine, Yokohama-shi,Kanagawa-ken, Japan

Takahiro Yamaji,

• Haruhara, Kotaro, The Jikei University School of Medcine, South Yarra, Victoria, Australia

Kotaro Haruhara,

• Ohki, Kohji, Yokohama City University Graduate School of Medicine, Yokohama-shi,Kanagawa-ken, Japan

Kohji Ohki,

• Uneda, Kazushi, Yokohama City University, Yokohama, Japan

Kazushi Uneda,

• Kobayashi, Ryu, Yokohama City University Graduate School of Medicine, Yokohama-shi,Kanagawa-ken, Japan

Ryu Kobayashi,

• Kinguchi, Sho, Yokohama City University, Yokohama, Japan

Sho Kinguchi,

• Toya, Yoshiyuki, Yokohama City University, Yokohama, Japan

Yoshiyuki Toya,

• Tamura, Kouichi, Yokohama City University Graduate School of Medicine, Yokohama-shi,Kanagawa-ken, Japan

Kouichi Tamura,

Background

Abnormal angiogenesis plays a major role in the development of early stage diabetic nephropathy. Vascular endothelial growth factor (VEGF) is a classical proangiogenic factor that regulates abnormal glomerular angiogenesis linked to glomerular hypertrophy in the early stage of diabetic nephropathy. Very recently, Leucine-rich α-2-glycoprotein-1 (LRG1), a novel proangiogenic factor expressed in endothelial cells, has been reported to be involved in the development of diabetic nephropathy. The aim of this study was to compare glomerular expression of the classical proangiogenic factor VEGF and novel proangiogenic factor LRG1 in the early stage of diabetic nephropathy.

Methods

We investigated intrarenal expression of VEGF and LRG1 in a mouse model of diabetes (db/db mouse) by immunohistochemistry and a laser capture microdissection method, and compared the changes in expression at 16 and 24 weeks of age to evaluate their association with diabetic nephropathy development.

Results

At 16 weeks, diabetic db/db mice exhibited glomerular hypertrophy with abnormal angiogenesis characterized by endothelial cell proliferation, which was concomitant with an increase in LRG1 expression of glomerular endothelial cells. However, glomerular VEGF expression was not increased at this early stage. At 24 weeks, the features of early diabetic nephropathy in db/db mice had developed further, along with further enhanced glomerular LRG1 expression. At this late stage, glomerular VEGF and fibrosis related-gene expression was also significantly increased compared with nondiabetic db/m mice.

Conclusion

These results suggest that LRG1 plays a pivotal role in the initial development of diabetic nephropathy by promoting abnormal angiogenesis, thereby suggesting that LRG1 is a potential preemptive therapeutic target of diabetic nephropathy.