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Article

Inhibitory effect of tumor necrosis factor‑α on the basolateral Kir4.1/Kir5.1 channels in the thick ascending limb during diabetes

  • Authors:
    • Guoyan Zhang
    • Zhiming Lv
    • Yang Zhao
    • Rui Chen
    • Xiangyu Zhan
    • Weiqun Wang
    • Hongyu Sui
  • View Affiliations / Copyright

    Affiliations: Department of Urology and Endocrinology, First Affiliated Hospital, Jiamusi University, Jiamusi, Heilongjiang 154003, P.R. China, Department of Physiology, Basic Medical College, Jiamusi University, Jiamusi, Heilongjiang 154007, P.R. China
  • Article Number: 1242
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    Published online on: September 1, 2021
       https://doi.org/10.3892/etm.2021.10677
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Abstract

Diabetic nephropathy is a major contributor to the morbidity and mortality of patients with diabetes. TNF‑α expression is elevated during diabetes and is implicated in the pathogenesis of diabetic nephropathy; however, its underlying molecular mechanisms remain unclear. The present study aimed to investigate the effect and molecular mechanism of TNF‑α on the basolateral inwardly rectifying potassium (Kir)4.1/Kir5.1 channels in the thick ascending limb (TAL) of rat kidneys using western blotting and the patch clamp technique to provide a theoretical basis for the cause of the decrease in kidney concentrating capacity during diabetes. The results demonstrated that urinary TNF‑α excretion and protein TNF‑α expression in the TAL increased and basolateral Kir4.1/Kir5.1 channel activity decreased during diabetes; however, diabetic rats exhibited amelioration of Kir4.1/Kir5.1 activity with a soluble TNF‑α antagonist, TNF receptor fusion protein (TNFR:Fc). These results suggested that TNF‑α inhibited the activity of the basolateral Kir4.1/Kir5.1 channel in the TAL of rat kidneys during diabetes. In addition, the protein expression levels of phospholipase A2 (PLA2) and cyclooxygenase‑2 (COX2) increased in diabetic rats, the effects of which deceased following treatment with TNFR:Fc compared with the diabetic group. Furthermore, an agonist of PLA2 (melittin) and COX2 production [prostaglandin E2 (PGE2)] inhibited the basolateral Kir4.1/Kir5.1 channels. Taken together, the results of the present study suggested that the inhibitory effect of TNF‑α on the basolateral Kir4.1/Kir5.1 channels in the TAL during diabetes is mediated by the PLA2/COX2/PGE2 signaling pathway.
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Copy and paste a formatted citation
Spandidos Publications style
Zhang G, Lv Z, Zhao Y, Chen R, Zhan X, Wang W and Sui H: Inhibitory effect of tumor necrosis factor‑α on the basolateral Kir4.1/Kir5.1 channels in the thick ascending limb during diabetes. Exp Ther Med 22: 1242, 2021.
APA
Zhang, G., Lv, Z., Zhao, Y., Chen, R., Zhan, X., Wang, W., & Sui, H. (2021). Inhibitory effect of tumor necrosis factor‑α on the basolateral Kir4.1/Kir5.1 channels in the thick ascending limb during diabetes. Experimental and Therapeutic Medicine, 22, 1242. https://doi.org/10.3892/etm.2021.10677
MLA
Zhang, G., Lv, Z., Zhao, Y., Chen, R., Zhan, X., Wang, W., Sui, H."Inhibitory effect of tumor necrosis factor‑α on the basolateral Kir4.1/Kir5.1 channels in the thick ascending limb during diabetes". Experimental and Therapeutic Medicine 22.5 (2021): 1242.
Chicago
Zhang, G., Lv, Z., Zhao, Y., Chen, R., Zhan, X., Wang, W., Sui, H."Inhibitory effect of tumor necrosis factor‑α on the basolateral Kir4.1/Kir5.1 channels in the thick ascending limb during diabetes". Experimental and Therapeutic Medicine 22, no. 5 (2021): 1242. https://doi.org/10.3892/etm.2021.10677
Copy and paste a formatted citation
x
Spandidos Publications style
Zhang G, Lv Z, Zhao Y, Chen R, Zhan X, Wang W and Sui H: Inhibitory effect of tumor necrosis factor‑α on the basolateral Kir4.1/Kir5.1 channels in the thick ascending limb during diabetes. Exp Ther Med 22: 1242, 2021.
APA
Zhang, G., Lv, Z., Zhao, Y., Chen, R., Zhan, X., Wang, W., & Sui, H. (2021). Inhibitory effect of tumor necrosis factor‑α on the basolateral Kir4.1/Kir5.1 channels in the thick ascending limb during diabetes. Experimental and Therapeutic Medicine, 22, 1242. https://doi.org/10.3892/etm.2021.10677
MLA
Zhang, G., Lv, Z., Zhao, Y., Chen, R., Zhan, X., Wang, W., Sui, H."Inhibitory effect of tumor necrosis factor‑α on the basolateral Kir4.1/Kir5.1 channels in the thick ascending limb during diabetes". Experimental and Therapeutic Medicine 22.5 (2021): 1242.
Chicago
Zhang, G., Lv, Z., Zhao, Y., Chen, R., Zhan, X., Wang, W., Sui, H."Inhibitory effect of tumor necrosis factor‑α on the basolateral Kir4.1/Kir5.1 channels in the thick ascending limb during diabetes". Experimental and Therapeutic Medicine 22, no. 5 (2021): 1242. https://doi.org/10.3892/etm.2021.10677
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