Abstract: SA-PO259
Transmembrane Protein 72, Expressed in the Distal Convoluted Tubule, May Play a Potential Role in Diabetic Kidney Disease
Session Information
- Diabetic Kidney Disease: Basic - 2
October 26, 2024 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Diabetic Kidney Disease
- 701 Diabetic Kidney Disease: Basic
Authors
- Xie, Jianteng, Guangdong Provincial People's Hospital, Guangzhou, Guangdong, China
- Lu, Min, Guangdong Provincial People's Hospital, Guangzhou, Guangdong, China
- Jia, Runli, Guangdong Provincial People's Hospital, Guangzhou, Guangdong, China
- Liu, Danfeng, Guangdong Provincial People's Hospital, Guangzhou, Guangdong, China
- Wang, Wenjian, Guangdong Provincial People's Hospital, Guangzhou, Guangdong, China
Background
Transmembrane protein 72 (TMEM72) is highly expressed in tubules of the kidney in patients with diabetic nephrology. This study is designed to explore the role and the potential mechanism of TMEM72 in the development of diabetic tubulopathy.
Methods
Serum TMEM72 concentration was tested in health control, patients with diabetes mellitus (DM) and diabetic kidney disease (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 in mice renal tubules. 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 HK2 cells following HG treatment.
Results
The concentration of serum TMEM72 was lower in DM and DKD groups compared to the health control (P<0.001). The expression of TMEM72 also 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, TMEM72 was markedly down-regulated in mouse tubular cell and HK-2 cells treated with high glucose. Overexpression or knock down of TMEM72 demonstrated a significant increased or decreased mitophagy in high glucose treated HK2. In vivo, tubules specific knock-out of TEME72 exhibited a significantly tubule injury evidenced by marked increase of KIM-1/Cr, NGAL/Cr, Albumin/Cr β-micro globin/Cr in the urine of mouse.
Conclusion
Our current study has revealed that TMEM72 may act as a novel participator in DKD by being involved in the renal tubular injury.
Funding
- Government Support – Non-U.S.