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Renoprotective Effect of the Recombinant Anti-IL-6R Fusion Proteins by Inhibiting JAK2/STAT3 Signaling Pathway in

Nanwen Zhang1,2, Qingmei Zheng3, Yaduan Wang3

  • 1School of Pharmacy, Department of Pharmacology, Fujian Medical University, Fuzhou, China.

Frontiers in Pharmacology
|May 31, 2021
PubMed

Insights

VHH-0031, an anti-interleukin-6 receptor fusion protein, protects kidneys from diabetic nephropathy by reducing inflammation and inhibiting the JAK2/STAT3 pathway. This offers a potential new treatment for diabetic kidney disease.

Area of Science:

  • Nephrology
  • Immunology
  • Molecular Biology

Background:

  • Diabetic nephropathy is a leading cause of end-stage renal disease.
  • Interleukin-6 (IL-6) is a key cytokine implicated in autoimmune disorders and kidney damage.
  • Targeting the IL-6 receptor presents a potential therapeutic strategy for diabetic kidney disease.

Purpose of the Study:

  • To investigate the renoprotective effects of VHH-0031, a novel anti-IL-6 receptor fusion protein, in models of diabetic nephropathy.
  • To elucidate the underlying mechanisms of VHH-0031's protective action in the kidney.

Main Methods:

  • VHH-0031 was administered to Goto-Kakizaki and STZ-induced diabetic rat models.
  • Renal function, inflammation, and morphology were assessed.
  • The JAK2/STAT3 signaling pathway in kidney tissues and mesangial cells was analyzed.
  • Mesangial cells were treated with VHH-0031 under high glucose conditions in vitro.

Main Results:

  • VHH-0031 treatment significantly alleviated renal inflammation, morphologic injury, and renal insufficiency in diabetic rats.
  • These protective effects were linked to the suppression of the JAK2/STAT3 signaling pathway.
  • In vitro, VHH-0031 inhibited mesangial cell proliferation and inflammation while inactivating the JAK2/STAT3 pathway under high glucose.

Conclusions:

  • VHH-0031 demonstrates significant renoprotective effects in diabetic nephropathy models.
  • The mechanism involves the inhibition of the IL-6 receptor (IL-6R)/JAK2/STAT3 pathway in glomerular mesangial cells.
  • VHH-0031 represents a promising therapeutic candidate for managing diabetic kidney disease.
Keywords:
GK ratIL-6JAK2/STAT3STZdiabetic nephropathy

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