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Isolation, Culture, and Characterization of Primary Dermal Fibroblasts from Human Keloid Tissue
Published on: July 28, 2023
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.
Abstract:
Systemic sclerosis is a typical fibrotic disease of unknown etiology that is characterized by abnormal fibroblast activation and excessive deposition of extracellular matrix. Unfortunately, effective therapeutic approaches are lacking. FGF21 plays a key role in mediating a variety of biological activities. However, its specific function in systemic sclerosis is unclear. In this study, we found that the expression of FGF21 was significantly downregulated in fibrotic skin tissue and in TGF-β-stimulated fibroblasts. Furthermore, our studies demonstrated that treatment with recombinant FGF21 in the skin significantly alleviated bleomycin-induced and TBRI-activated fibrosis and inhibited the activation of fibroblasts, whereas skin fibrosis was exacerbated by deletion of FGF21. Mechanistically, FGF21 inhibits the activity of CK2α and promotes the degradation of GLI2. In conclusion, these results indicate that FGF21 attenuates skin fibrosis through the CK2α/GLI2 signaling pathway and therefore may be a potential therapeutic target for systemic sclerosis.
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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