Kidney Week

Abstract: SA-PO514

Function of Protein X as a Novel Regulator of NADPH Oxidase 4 in 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

• Lee, Sae rom, Ewha Womans University, Seoul, Korea (the Republic of)

Sae rom Lee,

• Bae, Yun soo, Ewha Womans University, Seoul, Korea (the Republic of)

Yun soo Bae,

Background

Several lines of evidence indicate that NADPH oxidase (Nox)-derived excessive reactive oxygen species (ROS) play important role in diabetes complication such as diabetic nephropathy. It has been reprted that Nox4 isozyme is major source of ROS in pathological stage of kidney. Nox4, the isozyme highly expressed in kidney, is known to be constitutively active, but its activity is associated with diabetic nephropathy. We recently identified a novel regulator of Nox4, PX which interacts and activates Nox4. Here, we show that association of Nox4 with PX is involved in chronic kidney disease.

Methods

Eight week-old male wild type (WT), PX KO, Nox4 KO mice were subjected into the development of type I diabetes by injection of streptozotocin (STZ). Kidney tissues of the mice were analyzed with histological analyses, PAS-staining and collagen with immunohistochemistry (IHC) staining. Oxidative stress was assessed with urinary 8-isoprstane. Furthermore, renal functions were investigated by measurement of urinary albumin excretion and creatinine clearance rate (CCR).

Results

Mesangial expansion as a marker of glomerulosclerosis was reduced in PX KO and Nox4 KO mice. Albumin to creatinine ratio (ACR), urinary albumin excretion, and blood urea nitrogen (BUN) of protein X KO and Nox4 KO mice markedly decreased, compared to diabetic WT. Extracellular matrix (ECM) including collagen type I, type IV, TGF-β and α-SMA were significantly reduced in PX KO and Nox4 KO mice. Levels of H₂O₂ and urinary 8-isoprostane were suppressed in PX KO and Nox4 KO mice, compared to diabetic WT. To investigate clinical significance of PX-induced H₂O₂ generation, we evaluated the level of PX expression in type II diabetic patients. Interestingly, significantly elevated levels of PX were seen in type II diabetic patients. It strongly suggests that PX is involved in renal damage in type II diabetic patients.

Conclusion

In conclusion, PX as a Nox4 regulator plays important role in progression of diabetic nephropathy.