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Abstract: SA-PO0299

Potential Role of Transmembrane Protein 72, Expressed in the Distal Convoluted Tubule, in Diabetic Kidney Disease

Session Information

Category: Diabetic Kidney Disease

  • 701 Diabetic Kidney Disease: Basic

Authors

  • Xie, Jianteng, South China University of Technology School of Medicine, Guangzhou, Guangdong, China
  • Jia, Runli, South China University of Technology School of Medicine, Guangzhou, Guangdong, China
  • Liu, Danfeng, South China University of Technology School of Medicine, Guangzhou, Guangdong, China
  • Wang, Wenjian, Guangdong Provincial People's Hospital, Guangzhou, Guangdong, China
Background

Transmembrane protein 72(TMEM72) , which involved in normal kidney development and tumorigenesis in renal cell carcinoma, is highly expressed in tubules of the kidney. Whether there is a link between TMEM72 and the pathogenesis of renal tubular disease is unclear. This study is designed to explore the role and the potential mechanism of TMEM72 in the development of diabetic kidney disease(DKD).

Methods

Blood and urine sample were collected in health control and patients with DKD. Correlation between TMEM72 and renal function and urinary protein was analyzed. Collected normal renal tissue adjacent to renal tumors, as well as kidney biopsy samples from DKD. The variation trend of TMEM72 was determined by immunohistochemistry on kidney tissues from patients in different stage of DKD. Immunofluorescence staining was performed with TMEM72, SGLT2, NKCC2 and AQP2 to identify the expression site of TMEM72. To investigate the potential cellular pathway that TMEM72 was involved, an immunofluorescence test was performed with TMEM72, LAMP1, mito-tracker and calnexin in cultured distal convoluted tubule(DCT) epithelial cells. Western blot was used to detect the activity of TMEM72 in HK-s cells following HG treatment.

Results

The concentration of serum TMEM72 was higher in DKD groups when compared to the health control ( P < 0.001 ), same phenomenon can be seen in urine samples. In DKD population, there is a negative correlation between serum TMEM72 and eGFR ( P = 0.009, r = -0.347), patients with higher concentration of serum TMEM72 had lower eGFR. On the contrary, serum TMEM72 was positively correlated with uACR. The expression of TMEM72 decreased gradually in human kidney tissue of different stage of DKD following the progression of disease. Co-localization of TMEM72 and NKCC2 in immunofluorescence staining indicated that TMEM72 was mainly expressed in the lysosomes of distal convoluted tubule. In vitro, the expression of TMEM72 increases with rising glucose concentration and initially rises but then decreases with prolonged glucose stimulation in HK-2 cells.

Conclusion

Our current study has revealed that TMEM72 was mainly expressed in the lysosomes of distal convoluted tubule, and it may correlated with the incidence of DKD. Serum TMEM72 may act as a novel participator in DKD by being involved in the renal tubular injury.

Funding

  • Government Support – Non-U.S.

Digital Object Identifier (DOI)