Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
JCR Impact Factor (IF) – 1.727
Index Copernicus  – 152.95 pts
MNiSW – 40 pts

ISSN 1899–5276 (print)
ISSN 2451-2680 (online)
Periodicity – monthly

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Advances in Clinical and Experimental Medicine

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doi: 10.17219/acem/133494

Publication type: original article

Language: English

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FGF21 promotes wound healing of rat brain microvascular endothelial cells through facilitating TNF-α-mediated VEGFA and ERK1/2 signaling pathway

Weiting Chen1,A,D,F, Zhongen Shen2,A,B,E, Shuiqi Cai1,B,C, Long Chen1,C, Dabin Wang1,E

1 No. 1 Department of Orthopedics, The Third People’s Hospital, Cixi, China

2 Department of Anesthesiology, Cixi People Hospital, China


Background. Wound healing is an essential physiological process in recovery after microsurgery.
Objectives. To further understand the functions of fibroblast growth factor 21 (FGF21), the roles of this factor were examined and its correlations with inflammation, vascular endothelial growth factor A (VEGFA) and ERK1/2 signaling pathway activation were analyzed.
Material and Methods. Rat brain microvascular endothelial cells (RBMECs) were treated with interleukin (IL)-1β and used for the experiments. Cell Counting Kit-8 (CCK-8) was used to detect the cell viability of RBMECs after treatment with IL-1β (1 ng/mL) and FGF21 or VEGFA overexpression, while changes in apoptosis were measured through flow cytometry. Migration was checked through the scratch test. FGF21 and VEGFA RNA expression was assessed using reverse-transcription quantitative polymerase chain reaction (RT-qPCR), which was also used to examine RNA expression of Bcl-2, Bax and caspase-3. After IL-1β treatment and FGF21 overexpression, tumor necrosis factor alpha (TNF-α) and tumor growth factor β1 (TGF-β1) proteins level were observed with enzyme-linked immunosorbent assay (ELISA), which was also applied to check the expression of ERK1/2 after overexpression of FGF21 and VEGFA. PD98059 (50 μM), an ERK1/2 inhibitor, was used to examine the roles of ERK1/2 in regulating cell viability and apoptosis.
Results. The IL-1β treatment significantly decreased the viability of RBMECs and TGF-β1, but promoted cell apoptosis and TNF-α expression. FGF21 was downregulated by IL-1β treatment but its overexpression enhanced the viability of RBMECs and TGF-β1 and ERK1/2 protein levels, and attenuated cell apoptosis and TNF-α. Upregulated TNF-α restrained cell viability and apoptosis of RBMECs after FGF21 overexpression, and its upregulation not only suppressed FGF21, but also VEGFA. Moreover, VEGFA suppression by TNF-α increased cell viability and ERK1/2 protein levels, and suppressed the apoptosis of RBMECs through its upregulation. However, PD98059 obstructed the functions of FGF21 and VEGFA.
Conclusion. FGF21 promoted the cell viability of RBMECs through upregulating TNF-α-mediated VEGFA and ERK1/2 signaling.

Key words

VEGFA, FGF21, ERK1/2 signaling pathway, RBMEC

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