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Abstract: PO0937

NQO1 Deficiency Aggravates Renal Fibrosis Downregulating Through PI3-Complex Formation in Diabetic Nephropathy

Session Information

Category: Diabetic Kidney Disease

  • 601 Diabetic Kidney Disease: Basic

Authors

  • Hong, Geum-Lan, Chungnam National University, Daejeon, Daejeon, Korea (the Republic of)
  • Kim, Kyung-hyun, Chungnam National University, Daejeon, Daejeon, Korea (the Republic of)
  • Jung, Ju young, Chungnam National University, Daejeon, Daejeon, Korea (the Republic of)
Background

Diabetic nephropathy (DN) is one of cause leading to end-stage renal failure and the main pathological feature is renal fibrosis. An autophagy is a vital for cellular remodeling and intracellular homeostatsis and negatively regulate and limit renal fibrosis. NAD(P)H: quinone oxidoreductase 1 (NQO1) modulates the ratios of reduced/oxidaized nicotinamide nucleotide pools acting cytoprotective function. In this study, we examined the relationship between NQO1 and autophagy, and furthermore renal fibrosis alteration in NQO1-/- streptozotocin (STZ)-induced DN.

Methods

STZ (50 mg/kg) was injected to C57BL/6 (Wile type) and NQO1-/- mice to induce DN. After 12 weeks of STZ injection, renal pathology and the markers of autophagy and fibrosis were examined. To confirm the effects of NQO1 genes in DN progression in vitro, autophagy proteins and pro-fibrotic markers were assessed in silencing or overexpression of NQO1 on human proximal tubular cells (HK2) and human renal mesangial cells (HRMC).

Results

The STZ administration induced phenotypes of hyperglycemia and aggravated renal fibrosis in NQO1-/- mice. Futhermore, NQO1 deficiency reduced the autophagy down-regulating hVps34 and ATG14L of PI3-complex and induced pro-fibrotic genes including TGF-β1, Smad3, and MMP9, in vitro and in vivo. The fluorescence intensity of both hVps34 and ATG14L was reduced in siNQO1. However, NQO1-overexpression increased the expression of hVps35 and ATG14L but, reduced the expression of TGF-β1, Smad3 and MMP9.

Conclusion

NQO1 deficiency aggravated renal fibrosis mediating autophagy induction and phagophore formation. This results suggested that NQO1 may have a potential role for DN amelioration.

Funding

  • Government Support - Non-U.S.