FGF21 Ameliorates Fibroblasts Activation and Systemic Sclerosis by Inhibiting CK2α/GLI2 Signaling Axis

Yeyi Zheng1, Wenjie Gong2, Zhaohang Wu3

  • 1School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, People's Republic of China; Ningbo Key Laboratory of Skin Science, Ningbo College of Health Sciences, Ningbo, People's Republic of China.

Insights

Fibroblast Growth Factor 21 (FGF21) shows potential in treating systemic sclerosis, a fibrotic skin disease. FGF21 therapy reduced skin fibrosis by targeting the CK2α/GLI2 pathway.

Area of Science:

  • Fibrosis research
  • Dermatology
  • Endocrinology

Background:

  • Systemic sclerosis is a fibrotic disease with limited treatment options.
  • Abnormal fibroblast activation and extracellular matrix deposition characterize the condition.
  • The role of Fibroblast Growth Factor 21 (FGF21) in systemic sclerosis is not well understood.

Purpose of the Study:

  • To investigate the function and therapeutic potential of FGF21 in systemic sclerosis.
  • To elucidate the molecular mechanisms by which FGF21 affects skin fibrosis.

Main Methods:

  • Assessed FGF21 expression in fibrotic skin and TGF-β-stimulated fibroblasts.
  • Administered recombinant FGF21 in bleomycin-induced and TBRI-activated skin fibrosis models.
  • Examined the effects of FGF21 deletion on skin fibrosis.
  • Investigated FGF21's impact on CK2α activity and GLI2 degradation.

Main Results:

  • FGF21 expression was significantly downregulated in fibrotic skin and activated fibroblasts.
  • Recombinant FGF21 treatment alleviated skin fibrosis and inhibited fibroblast activation.
  • FGF21 deletion exacerbated skin fibrosis.
  • FGF21 was found to inhibit CK2α activity and promote GLI2 degradation.

Conclusions:

  • FGF21 plays a protective role in attenuating skin fibrosis.
  • FGF21 acts through the CK2α/GLI2 signaling pathway to inhibit fibroblast activation and matrix deposition.
  • FGF21 represents a potential therapeutic target for treating systemic sclerosis.

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