FGF21 promotes migration and differentiation of epidermal cells during wound healing via SIRT1‐dependent autophagy

Chen, Xixi; Tong, Gaozan; Fan, Junfu; Shen, Yingjie; Wang, Nan; Gong, Wenjie; Hu, Zijing; Zhu, Kunxuan; Li, Xiaokun; Jin, Litai; Cong, Weitao; Xiao, Jian; Zhu, Zhongxin

doi:10.1111/bph.15701

Cited by 29 publications

(15 citation statements)

References 66 publications

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“…FGF21 has been reported to act in a paracrine fashion to promote cell migration and differentiation during wound healing and to act in a dual paracrine fashion to increase KGF expression, promoting fibroblast activation in skin fibrosis. These findings are consistent with the mechanism of action of FGF21 observed in this study [ 45 , 46 ]. FGF21 is mainly secreted by the liver and adipose tissue, with these tissues being important sources of FGF21 in some diseases [ 47 ].…”

Section: Discussionsupporting

confidence: 93%

Suppression of Cutibacterium acnes-Mediated Inflammatory Reactions by Fibroblast Growth Factor 21 in Skin

Shen

Zhang

et al. 2022

IJMS

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Cutibacterium acnes (C. acnes) is a common commensal bacterium that is closely associated with the pathogenesis of acne. Fibroblast growth factor 21 (FGF21), as a favorable regulator of glucose and lipid metabolism and insulin sensitivity, was recently shown to exert anti-inflammatory effects. The role and mechanism of FGF21 in the inflammatory reactions induced by C. acnes, however, have not been determined. The present study shows that FGF21 in the dermis inhibits epidermal C. acnes-induced inflammation in a paracrine manner while it functions on the epidermal layer through a receptor complex consisting of FGF receptor 1 (FGFR1) and β-Klotho (KLB). The effects of FGF21 in heat-killed C. acnes-induced HaCaT cells and living C. acnes-injected mouse ears were examined. In the presence of C. acnes, FGF21 largely counteracted the activation of Toll-like receptor 2 (TLR2), the downstream nuclear factor-κB (NF-κB), and mitogen-activated protein kinase (MAPK) signaling pathways induced by C. acnes. FGF21 also significantly reduced the expression of proinflammatory cytokines, including interleukin (IL)-1β, IL-6, IL-8, and tumor necrosis factor (TNF)-α. Taken together, these findings indicate that FGF21 suppresses C. acnes-induced inflammation and might be used clinically in the management and treatment of acne.

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Section: Discussionsupporting

confidence: 93%

Suppression of Cutibacterium acnes-Mediated Inflammatory Reactions by Fibroblast Growth Factor 21 in Skin

Shen

Zhang

et al. 2022

IJMS

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“…Autophagy has recently been found to play an essential role in the regulation of many types of cell migration [35][36][37], but the related mechanisms are not fully understood. Bressan and Saghatelyan showed that AMPKinduced autophagy is a key regulator of cell migration and plays an important role in the recycling of the focal adhesion molecule paxillin [38].…”

Section: Discussionmentioning

confidence: 99%

Autophagy Modulates the Migration of Retinal Pericytes Induced by Advanced Glycation End Products

Lin

Zhou

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Retinal pericyte migration occurs in the early stage of diabetic retinopathy (DR), which is one of the important causes of pericyte loss. Autophagy has been found to play essential roles in the regulation of many types of cell migration. In this study, we explored the relationship between autophagy and retinal pericyte migration. In diabetic rats, the retinas became thinner, and the level of autophagy in each cell layer increased. In the primary culture of bovine retinal pericytes, we found that advanced glycation end products (AGEs) increased the migratory cell ability without influencing cell viability, which also increased the phosphorylation of focal adhesion kinase (FAK) and the expression of matrix metalloproteinase (MMP)-2 and decreased the expression of vinculin. AGEs-induced retinal pericyte autophagy and the inhibition of autophagy with chloroquine significantly inhibited cell migration, reversed AGEs-induced FAK phosphorylation, and changed vinculin and MMP-2 protein expression. These results provide a new insight into the migration mechanism of retinal pericytes. The early control of autophagy has a potential effect on regulating pericyte migration, which may contribute to keeping the integrity of retinal vessels in DR.

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“…Previous studies identified that SIRT1 is downregulated in PD, and upregulating SIRT1 is neuroprotective against MPTP-mediated neurotoxicity (Singh et al, 2017 ). Of interest, more recent studies have shown that the effects of FGF21 are highly related to SIRT1 expression (Chen et al, 2021 ), and SIRT promoted FGF21 sensitivity neuronal cells (Matsui et al, 2018 ). We then examined the SIRT1 expression in PD models, and our results showed that FGF21 significantly upregulated the SIRT1 expression and inhibited the activation of the NF-κB pathway both in vivo and in vitro .…”

Section: Discussionmentioning

confidence: 99%

Fibroblast Growth Factor 21 Modulates Microglial Polarization That Attenuates Neurodegeneration in Mice and Cellular Models of Parkinson's Disease

Yang

Wang

Deng

et al. 2021

Front. Aging Neurosci.

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Microglial polarization and the subsequent neuroinflammatory response were identified as key contributors to the progress of Parkinson's disease (PD). Researchers have shown that fibroblast growth factor 21 (FGF21) plays multiple biological functions, including anti-inflammation and neuroprotection. However, the knowledge of FGF21 on microglial polarization in PD in vivo is far from completion. In this study, both in vivo and in vitro models were used to investigate whether FGF21 enhances the brain function by modulating microglial polarization in PD. The protective effects of FGF21 in vivo were conducted using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced PD mice model alongside intraperitoneally received FGF21. A behavioral test battery and tyrosine hydroxylase (TH) immunohistochemistry were conducted to evaluate the neuronal function and nigrostriatal tract integrity. Immunofluorescence assay and Western blot were used to examine M1/M2 microglial polarization. Then, a microglia-neuron co-culture system was adopted in vitro to identify the underlying molecular mechanisms of FGF21. The results showed that FGF21 significantly alleviated motor and cognitive impairment in mice with PD. FGF21 also protected TH-positive neuron cells in the striatum and midbrain. Mechanistically, FGF21 suppressed M1 microglial polarization and the subsequent mRNA expression of pro-inflammatory factors while promoting M2 microglial polarization with increasing anti-inflammatory factors in mice with PD. Furthermore, sirtuin 1 (SIRT1) and the nuclear factor-kappa B (NF-κB) pathway were involved in the FGF21-induced M2 microglial polarization. Conversely, SIRT1 inhibitor EX527 significantly prevented both the FGF21-induced SIRT1 expression and M2 microglial polarization. Moreover, FGF21 pretreatment of microglia significantly prevented neuronal cell apoptosis in a microglia-neuron co-culture system. In conclusion, our data demonstrate that FGF21 exerted its protective effects in the pathology of PD through SIRT1/NF-κB pathway-mediated microglial polarization. Given the safety record of human clinical trials, FGF21 could be a promising therapy for clinical trials to ameliorate motor and nonmotor deficits in patients with PD.

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FGF21 promotes migration and differentiation of epidermal cells during wound healing via SIRT1‐dependent autophagy

Cited by 29 publications

References 66 publications

Suppression of Cutibacterium acnes-Mediated Inflammatory Reactions by Fibroblast Growth Factor 21 in Skin

Suppression of Cutibacterium acnes-Mediated Inflammatory Reactions by Fibroblast Growth Factor 21 in Skin

Autophagy Modulates the Migration of Retinal Pericytes Induced by Advanced Glycation End Products

Fibroblast Growth Factor 21 Modulates Microglial Polarization That Attenuates Neurodegeneration in Mice and Cellular Models of Parkinson's Disease

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