Dataset Information

HIF-1? promotes the keloid development through the activation of TGF-?/Smad and TLR4/MyD88/NF-?B pathways.

ABSTRACT: A keloid is defined as an overgrowth of the dense fibrous tissues that form around a wound. Since they destroy the vascular network, keloid tissues often exhibit anoxic conditions. Hypoxia-inducible factor-1? (HIF-1?) is a core factor that mediates hypoxia stress responses and regulates the hypoxic cellular and biological behaviors. In this study, we found that the expression level of HIF-1? in keloid tissue was significantly higher than that in the normal skin tissue. Hypoxia-induced HIF-1? expression significantly inhibited cellular apoptosis and promoted cellular proliferation in keloid fibroblasts but not in normal fibroblasts. Specifically, HIF-1? activated the TGF-?/Smad and TLR4/MyD88/NF-?B pathways, and the interaction of these two pathways may promote the development of keloids. Moreover, in vivo experiments showed that the inhibition of HIF-1? significantly reduced the growth of keloids.

SUBMITTER: Lei R

PROVIDER: S-EPMC6927730 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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HIF-1α promotes the keloid development through the activation of TGF-β/Smad and TLR4/MyD88/NF-κB pathways.

Lei Rui R Li Jian J Liu Feng F Li Weihan W Zhang Shizhen S Wang Yang Y Chu Xi X Xu Jinghong J

Cell cycle (Georgetown, Tex.) 20191023 23

A keloid is defined as an overgrowth of the dense fibrous tissues that form around a wound. Since they destroy the vascular network, keloid tissues often exhibit anoxic conditions. Hypoxia-inducible factor-1α (HIF-1α) is a core factor that mediates hypoxia stress responses and regulates the hypoxic cellular and biological behaviors. In this study, we found that the expression level of HIF-1α in keloid tissue was significantly higher than that in the normal skin tissue. Hypoxia-induced HIF-1α exp ...[more]

PMID: 31645185

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Project description:BackgroundJianpi Yangxue Qufeng Compound (JPYXQFC) is a Chinese medicine widely used in the clinical treatment of atopic dermatitis (AD) and has a significantly therapeutic effect. However, the mechanism of JPYXQFC in AD has been not understood clearly.ObjectiveThis study aimed to explore the effect of JPYXQFC on AD model cells and rats by regulating TLR4/MyD88/NF-κB signaling pathway.MethodsThe rats (n > 5) were given JPYXQFC decoction orally twice a day for three days, and their abdominal aortic blood was collected. HaCaT cell proliferation rate was tested by cell counting kit-8 (CCK-8) assays. We induced AD rat model through 2, 4-dinitrofluorobenzene (DNFB). AD rats were given oral JPYXQFC decoction and cetirizine (positive control). HaCaT cells were pretreated with JPYXQFC drug serum or cetirizine for 0.5 h and then stimulated with TNF-α/IFN-γ for 1 h. The mRNA levels of TLR4, MyD88, NF-κB, IL-4, IL-13, MCP1, TNF-α and TSLP were detected by quantitative real-time PCR (Q-RT-PCR), and TLR4/MyD88/NF-κB pathway protein expression was tested by Western blot. The total serum levels of immunoglobulin E (IgE), thymus and activation regulated chemokine/chemokine (C-C motif) ligand 17 (TARC/CCL17) were detected by enzyme-linked immunosorbent assay (ELISA). The epidermal thickness was detected by hematoxylin and eosin (HE) staining. The dermatitis area and score were measured by a ruler and a four-point scoring method, respectively.ResultsJPYXQFC significantly inhibited mRNA and protein expression of the TLR4/MyD88/NF-κB pathway and Histone H3 in TNF-α/IFN-γ-induced HaCaT cells and DNFB-induced rats, decreased the mRNA of IL-4, IL-13, MCP1, CCL22, TSLP and the level of AD-related genes IgE and TAEC/CCL17 of TNF-α/IFN-γ-induced HaCaT cells. Meanwhile, JPYXQFC significantly reduced the dermatitis area and dermatitis score in DNFB-induced rats, inhibited the levels of pro-inflammatory cytokines IL-6 and TNF-α, and upregulated FLG, as well as inhibited the levels of IgE and TARC/CCL17 in the serum of AD rats.ConclusionJPYXQFC alleviates AD by inhibiting the activation of TLR4/MyD88/NF-κB pathway.

Dataset Information

HIF-1? promotes the keloid development through the activation of TGF-?/Smad and TLR4/MyD88/NF-?B pathways.

Publications

HIF-1α promotes the keloid development through the activation of TGF-β/Smad and TLR4/MyD88/NF-κB pathways.

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