Adiponectin Regulates Cutaneous Wound Healing by Promoting Keratinocyte Proliferation and Migration via the ERK Signaling Pathway

Abstract Background: Timely and sufficient recruitment of M1 macrophages and M2 polarization are necessary for fibrous repair during cutaneous wound healing. The inherent mechanism of how M2 polarization mediate wound healing is worth exploring and illustrating. Abnormally up-regulated connective tissue growth factor (CTGF) is closely related with multiple organ fibrosis, including cardiac, pulmonary, hepatic, renal, and cutaneous fibrosis. Previous studies have reported that M2-polarized macrophages contribute to hepatic and renal fibrosis by secreting CTGF. It is worth discussing if M2 macrophages regulate fibrosis through secreting CTGF in cutaneous wound healing.Methods: We established the murine full-thickness excisional wound model and inhibited macrophages during proliferation phase (mainly M2 and M1-M2 polarization) with clodronate liposomes to analyze how M2 macrophages mediate wound healing rates, collagen deposition, collagen 1/3 expression, and Ki67 expression in vivo. Furthermore, M2 polarization was induced by IL-4 and in vitro. F4/80+CD206+ M2 macrophages were measured by flow cytometry. The morphological characteristics were observed. Secretion of IL-6, TNF-α, IL-10, TGF-β1, and CTGF was tested by ELISA. CTGF gene of M2 was blocked using siCTGF. Effects of M2 on proliferation and migration of fibroblasts were detected by CCK8 and cellular wound healing assay. Protein level of AKT, ERK1/2, and STAT3 pathway were assessed by western blotting.Results: Depletion of macrophages at proliferation phase (mainly M2 and M1-M2 polarization) resulted in delayed cutaneous wound closure and down-regulation of wound healing rates, collagen deposition, collagen 1/3 expression, and Ki67 expression. M2 polarization was induced, which producing more CTGF, TGF-β1, and IL-6, as well as less TNF-α and IL-10. Blockade of CTGF in M2 macrophages deactivated fibroblast proliferation and migration. Addition of recombinant CTGF restored the promotional effects of M2 macrophages on fibroblast proliferation and migration. Blockade of CTGF in M2 mediate fibroblasts via down-regulating AKT, ERK1/2, and STAT3 signaling pathway.Conclusion: Our research, for the first time, indicated that M2-polarized macrophages promoted cutaneous wound healing by secreting CTGF, which further mediating proliferation and migration of fibroblasts via AKT, ERK1/2, and STAT3 signaling pathway.

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Gypenoside LXXV Promotes Cutaneous Wound Healing In Vivo by Enhancing Connective Tissue Growth Factor Levels Via the Glucocorticoid Receptor Pathway

Molecules ◽

10.3390/molecules24081595 ◽

2019 ◽

Vol 24 (8) ◽

pp. 1595 ◽

Cited By ~ 7

Author(s):

Sungjoo Park ◽

Eunsu Ko ◽

Jun Hyoung Lee ◽

Yoseb Song ◽

Chang-Hao Cui ◽

...

Keyword(s):

Wound Healing ◽

Growth Factor ◽

Connective Tissue ◽

Wound Closure ◽

Tissue Growth ◽

Cutaneous Wound Healing ◽

Cutaneous Wound ◽

And Migration ◽

Proliferation And Migration

Cutaneous wound healing is a well-orchestrated event in which many types of cells and growth factors are involved in restoring the barrier function of skin. In order to identify whether ginsenosides, the main active components of Panax ginseng, promote wound healing, the proliferation and migration activities of 15 different ginsenosides were tested by MTT assay and scratched wound closure assay. Among ginsenosides, gypenoside LXXV (G75) showed the most potent wound healing effects. Thus, this study aimed to investigate the effects of G75 on wound healing in vivo and characterize associated molecular changes. G75 significantly increased proliferation and migration of keratinocytes and fibroblasts, and promoted wound closure in an excision wound mouse model compared with madecassoside (MA), which has been used to treat wounds. Additionally, RNA sequencing data revealed G75-mediated significant upregulation of connective tissue growth factor (CTGF), which is known to be produced via the glucocorticoid receptor (GR) pathway. Consistently, the increase in production of CTGF was confirmed by western blot and ELISA. In addition, GR-competitive binding assay and GR translocation assay results demonstrated that G75 can be bound to GR and translocated into the nucleus. These results demonstrated that G75 is a newly identified effective component in wound healing.

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Activin B Promotes BMSC-Mediated Cutaneous Wound Healing by Regulating Cell Migration via the JNK—ERK Signaling Pathway

Cell Transplantation ◽

10.3727/096368913x666999 ◽

2014 ◽

Vol 23 (9) ◽

pp. 1061-1073 ◽

Cited By ~ 30

Author(s):

Min Zhang ◽

Li Sun ◽

Xueer Wang ◽

Shixuan Chen ◽

Yanan Kong ◽

...

Keyword(s):

Wound Healing ◽

Cell Migration ◽

Signaling Pathway ◽

Erk Signaling ◽

Cutaneous Wound Healing ◽

Cutaneous Wound

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Eden Model Simulation of Re-Epithelialization and Angiogenesis of an Epidermal Wound

Processes ◽

10.3390/pr6110207 ◽

2018 ◽

Vol 6 (11) ◽

pp. 207

Author(s):

Ephraim Agyingi ◽

Luke Wakabayashi ◽

Tamas Wiandt ◽

Sophia Maggelakis

Keyword(s):

Model Simulation ◽

Cutaneous Wound Healing ◽

Epidermal Stem Cells ◽

Wound Edge ◽

Wound Area ◽

Cutaneous Wound ◽

Simulation Results ◽

Eden Model ◽

And Migration ◽

Proliferation And Migration

Among the vital processes of cutaneous wound healing are epithelialization and angiogenesis. The former leads to the successful closure of the wound while the latter ensures that nutrients are delivered to the wound region during and after healing is completed. These processes are regulated by various cytokines and growth factors that subtend their proliferation and migration into the wound region until full healing is attained. Wound epithelialization can be enhanced by the administration of epidermal stem cells (ESC) or impaired by the presence of an infection. This paper uses the Eden model of a growing cluster to independently simulate the processes of epithelialization and angiogenesis in a cutaneous wound for different geometries. Further, simulations illustrating bacterial infection are provided. Our simulation results demonstrate contraction and closure for any wound geometry due to a collective migration of epidermal cells from the wound edge in fractal form and the diffusion of capillary sprouts with the laying down of capillary blocks behind moving tips into the wound area.

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Sodium humate accelerates cutaneous wound healing by activating TGF-β/Smads signaling pathway in rats

Acta Pharmaceutica Sinica B ◽

10.1016/j.apsb.2016.01.009 ◽

2016 ◽

Vol 6 (2) ◽

pp. 132-140 ◽

Cited By ~ 6

Author(s):

Yuanyuan Ji ◽

Aijun Zhang ◽

Xiaobin Chen ◽

Xiaoxia Che ◽

Kai Zhou ◽

...

Keyword(s):

Wound Healing ◽

Signaling Pathway ◽

Cutaneous Wound Healing ◽

Cutaneous Wound ◽

Sodium Humate

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Calcium-sensing receptor promotes tumor proliferation and migration in human intrahepatic cholangiocarcinoma by targeting ERK signaling pathway

European Journal of Pharmacology ◽

10.1016/j.ejphar.2020.172915 ◽

2020 ◽

Vol 872 ◽

pp. 172915

Author(s):

Yu Fang ◽

Liu Liu ◽

Shaojun Liu ◽

Lei Hu ◽

Wei Cai ◽

...

Keyword(s):

Signaling Pathway ◽

Intrahepatic Cholangiocarcinoma ◽

Erk Signaling ◽

Tumor Proliferation ◽

Calcium Sensing Receptor ◽

Calcium Sensing ◽

And Migration ◽

Proliferation And Migration

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SOX2 Epidermal Overexpression Promotes Cutaneous Wound Healing via Activation of EGFR/MEK/ERK Signaling Mediated by EGFR Ligands

Journal of Investigative Dermatology ◽

10.1016/j.jid.2019.02.004 ◽

2019 ◽

Vol 139 (8) ◽

pp. 1809-1820.e8 ◽

Cited By ~ 6

Author(s):

Akihiko Uchiyama ◽

Subhashree Nayak ◽

Rose Graf ◽

Michael Cross ◽

Kowser Hasneen ◽

...

Keyword(s):

Wound Healing ◽

Erk Signaling ◽

Cutaneous Wound Healing ◽

Cutaneous Wound ◽

Egfr Ligands

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BCKDK Promotes Epithelial Ovarian Cancer Proliferation and Migration by Activating the MEK/ERK Signaling Pathway

10.21203/rs.3.rs-643743/v1 ◽

2021 ◽

Author(s):

Huashun Li ◽

Dongyang Yu ◽

Lianbing Li ◽

Juanjuan Xiao ◽

Yijian Zhu ◽

...

Keyword(s):

Ovarian Cancer ◽

Epithelial Ovarian Cancer ◽

Signaling Pathway ◽

Western Blotting ◽

Molecular Mechanisms ◽

Cell Transformation ◽

Gynecologic Cancer ◽

Erk Signaling ◽

And Migration ◽

Proliferation And Migration

Abstract Background: Ovarian cancer is the most fatal gynecologic cancer, and epithelial ovarian cancer (EOC) is the most common type. The branched-chain α-keto acid dehydrogenase kinase (BCKDK) plays an important role in many serious human diseases, including cancers. Its function in promoting cell proliferation and migration has been reported in various cancers. However, the biological role of BCKDK and its molecular mechanisms underlying EOC initiation and progression are unclear.Methods: First, the expression level of BCKDK in EOC cell lines or tissues was determined using tissue microarray (TMA)-based immunohistochemistry or western blotting. Then, growth curve analysis, anchorage-independent cell transformation assays, wound healing assays, cell migration assays, and tumor xenografts were used to test whether BCKDK could promote cell transformation or metastasis. Finally, the signaling pathways involved in this process were investigated by western blotting or immunoprecipitation.Results: We found that the expression of BCKDK was upregulated in EOC tissues and that high expression of BCKDK was correlated with an advanced pathological grade in patients. The ectopic overexpression of BCKDK promoted the proliferation and migration of EOC cells, and the knockdown of BCKDK with shRNAs inhibited the proliferation and migration of EOC ex vivo and in vivo. Moreover, BCKDK promoted EOC proliferation and migration by activating MEK.Conclusions: Our results demonstrate that BCKDK promotes EOC proliferation and migration by activating the MEK/ERK signaling pathway. Targeting the BCKDK-MEK axis may provide a new therapeutic strategy for treating patients with EOC.

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Exosomes Derived from Dental Pulp Stem Cells Accelerate Cutaneous wound Healing by Enhancing Angiogenesis via Cdc42/p38 MAPK Pathway

10.21203/rs.3.rs-985814/v1 ◽

2021 ◽

Author(s):

Ziyu Zhou ◽

Jianmao Zheng ◽

Danle Lin ◽

Yanan Chen ◽

Xiaoli Hu

Keyword(s):

Stem Cells ◽

Wound Healing ◽

Signaling Pathway ◽

P38 Mapk ◽

Dental Pulp ◽

Mapk Pathway ◽

Mapk Signaling ◽

Cutaneous Wound Healing ◽

Cutaneous Wound ◽

Protein Levels

Abstract Background: Skin wound healing is a common challenging clinical problem and need advanced treatment strategies. Here, we investigated the therapeutic effects of exosomes derived from dental pulp stem cells (DPSC-Exos) on cutaneous wound healing and the underlying mechanisms. Methods: The effects of DPSC-Exos on cutaneous wound healing in mice were examined by measuring wound closure rates, histological and immunohistochemical analysis. A series of functional assays were performed to evaluate the effects of DPSC-Exos on the angiogenic activities of human umbilical vein endothelial cells (HUVECs) in vitro. TMT-based quantitative proteomic analysis of DPSCs and DPSC-Exos was performed. Gene ontology (GO) and KEGG pathway enrichment analysis were used to evaluate biological functions and pathways for the differentially expressed proteins in DPSC-Exos. Western blot was used to assess the protein levels of Cdc42 and p38 in DPSC-Exos-induced angiogenesis of HUVECs. SB203580, a p38 MAPK signaling pathway inhibitor, was employed to verify the role of p38 MAPK pathway in these processes.Results: Histological and immunohistochemical staining revealed that DPSC-Exos accelerated wound healing by improving neovascularization. DPSC-Exos augmented the migration, proliferation, and capillary formation capacity of HUVECs. Proteomic data demonstrated that proteins contained in DPSC-Exos regulated vasculature development and angiogenesis. Pathway analysis showed that proteins expressed in DPSC-Exos were involved in several pathways including MAPK pathway. Western blotting demonstrated that DPSC-Exos increased the protein levels of Cdc42 and phosphorylation of p38 in HUVECs. SB203580 suppressed the angiogenesis of HUVECs induced by DPSC-Exos.Conclusions: DPSC-Exos could accelerate cutaneous wound healing by enhancing the angiogenic properties of HUVECs via Cdc42/p38 MAPK signaling pathway.

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