Mechanism of NHX1 Inhibiting TRPV5-Mediated Podocyte Injury in Diabetic Nephropathy
American Journal of Clinical and Experimental Medicine
Volume 6, Issue 5, September 2018, Pages: 113-117
Received: Dec. 5, 2018;
Published: Dec. 6, 2018
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Rui Li, Department of Nephrology, Binzhou People's Hospital, Binzhou, China
Qingfen Wang, Department of Nephrology, Binzhou People's Hospital, Binzhou, China
Xiaochun Niu, Department of Nephrology, Binzhou People's Hospital, Binzhou, China
Ruirui Xu, Department of Nephrology, Binzhou People's Hospital, Binzhou, China
To observe the effect of high glucose stimulation on the expression of guanylate exchange factor NHX1 in mouse kidney cells, and to explore the role of NHX1 in high glucose-induced podocyte injury and its possible molecular mechanism. The expression of NHX1 in podocytes of diabetic nephropathy patients was observed by immunofluorescence staining and laser confocal microscopy. The immortalized podocytes were cultured in vitro, and the podocytes were stimulated with high glucose for 48 h. RT-PCR, Western blot and immunization were used. Fluorescence detection of mRNA and protein expression of NHX1 in podocytes stimulated by high glucose; Western blot, immunofluorescence and scratch assay were used to detect the expression of NHX1 and the expression of podocin, the activity of podocytes and the nuclear access of TRPV5. The transcription of the target gene downstream of TRPV5 was detected by RT-PCR. NHX1 expression was significantly decreased in podocytes and high glucose-stimulated podocytes of diabetic nephropathy patients (P<0.05). After silencing NHX1, podocyte marker protein podocin expression was significantly decreased and podocyte activity was increased. The nuclear translocation of TRPV5 increased, and the transcription of the target gene downstream of TRPV5 increased (P < 0.05). In contrast, the expression of overexpressed NHX1 group was significantly increased, the activity of podocytes was decreased, the nuclear access of TRPV5 was decreased, and the transcription of the target gene downstream of TRPV5 was decreased (P<0.05). NHX1 may reduce podocyte injury in diabetic nephropathy by inhibiting TRPV5 entry into the nucleus.
Mechanism of NHX1 Inhibiting TRPV5-Mediated Podocyte Injury in Diabetic Nephropathy, American Journal of Clinical and Experimental Medicine.
Vol. 6, No. 5,
2018, pp. 113-117.
Zhou Z, Wan J, Hou X, Geng J, Li X, Bai X. Correction: MicroRNA-27a promotes podocyte injury via PPARgamma-mediated beta-catenin activation in diabetic nephropathy. Cell death & disease. 2018; 9 (6): 652.
Chen X, Zhao L, Xing Y, Lin B. Down-regulation of microRNA-21 reduces inflammation and podocyte apoptosis in diabetic nephropathy by relieving the repression of TIMP3 expression. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. 2018; 108: 7-14.
Zhong F, Chen H, Xie Y, Azeloglu EU, Wei C, Zhang W, et al. Protein S Protects against Podocyte Injury in Diabetic Nephropathy. Journal of the American Society of Nephrology: JASN. 2018; 29 (5): 1397-410.
Bai X, Geng J, Li X, Wan J, Liu J, Zhou Z, et al. Long Noncoding RNA LINC01619 Regulates MicroRNA-27a/Forkhead Box Protein O1 and Endoplasmic Reticulum Stress-Mediated Podocyte Injury in Diabetic Nephropathy. Antioxidants & redox signaling. 2018; 29 (4): 355-76.
Fujita Y, Tominaga T, Abe H, Kangawa Y, Fukushima N, Ueda O, et al. An adjustment in BMP4 function represents a treatment for diabetic nephropathy and podocyte injury. Scientific reports. 2018; 8 (1): 13011.
Zhang Z, Li X, Liu L, Sun J, Wang X, Zhao Z, et al. Tiaolipiwei Acupuncture Reduces Albuminuria by Alleviating Podocyte Lesions in a Rat Model of Diabetic Nephropathy. Evidence-based complementary and alternative medicine: eCAM. 2018; 2018: 1913691.
He Y, Zhang M, Wu Y, Jiang H, Fu H, Cai Y, et al. Aberrant activation of Notch-1 signaling inhibits podocyte restoration after islet transplantation in a rat model of diabetic nephropathy. Cell death & disease. 2018; 9 (10): 950.
Zhang Y, Chen X, Yuan L, Wu J, Guo N, Liu J. Down-regulation of IRAK1 attenuates podocyte apoptosis in diabetic nephropathy through PI3K/Akt signaling pathway. Biochemical and biophysical research communications. 2018; 506 (3): 529-35.
Lei X, Zhang L, Li Z, Ren J. Astragaloside IV/lncRNA-TUG1/TRAF5 signaling pathway participates in podocyte apoptosis of diabetic nephropathy rats. Drug design, development and therapy. 2018; 12: 2785-93.
Wang Y, Li H, Song SP. beta-Arrestin 1/2 Aggravates Podocyte Apoptosis of Diabetic Nephropathy via Wnt/beta-Catenin Pathway. Medical science monitor: international medical journal of experimental and clinical research. 2018; 24: 1724-32.
Pan Y, Jiang S, Hou Q, Qiu D, Shi J, Wang L, et al. Dissection of Glomerular Transcriptional Profile in Patients With Diabetic Nephropathy: SRGAP2a Protects Podocyte Structure and Function. Diabetes. 2018; 67 (4): 717-30.
Wang XB, Zhu H, Song W, Su JH. Gremlin Regulates Podocyte Apoptosis via Transforming Growth Factor-beta (TGF-beta) Pathway in Diabetic Nephropathy. Medical science monitor: international medical journal of experimental and clinical research. 2018; 24: 183-9.
Lv Z, Hu M, Fan M, Li X, Lin J, Zhen J, et al. Podocyte-specific Rac1 deficiency ameliorates podocyte damage and proteinuria in STZ-induced diabetic nephropathy in mice. Cell death & disease. 2018; 9 (3): 342.
Wang X, Gao L, Lin H, Song J, Wang J, Yin Y, et al. Mangiferin prevents diabetic nephropathy progression and protects podocyte function via autophagy in diabetic rat glomeruli. European journal of pharmacology. 2018; 824: 170-8.
Tung CW, Hsu YC, Shih YH, Chang PJ, Lin CL. Glomerular mesangial cell and podocyte injuries in diabetic nephropathy. Nephrology (Carlton). 2018; 23 Suppl 4: 32-7.