scholarly journals Wnt/β-catenin Signaling Pathway Promotes Transdifferentiation from Fetal Skin Fibroblasts to Keratinocyte-like Cells

2021 ◽  
Author(s):  
Hongqing Zhao ◽  
Xinzhu Liu ◽  
Jiachen Sun ◽  
Yuezeng Niu ◽  
Kun Zhang ◽  
...  
Keyword(s):  
Wound Healing ◽  
Signaling Pathway ◽  
Wound Repair ◽  
Culture Conditions ◽  
Skin Fibroblasts ◽  
Fetal Skin ◽  
Protein Levels ◽  
Conventional Culture ◽  
Cellular Events ◽  
Proliferation And Differentiation

Abstract Background: Wound healing is a dynamic, sequential,and complex physiological process, including a variety of cellular events, such as proliferation, adhesion, chemotaxis, and apoptosis. Skin fibroblasts and keratinocytes are the two most important cells involved in wound repair, and Relying on the proliferation and differentiation of keratinocytes to form epithelium to completely cover the wound is the most ideal result for wound repair, so expanding the source of keratinocytes is a huge challenge. In this study, we examined the phenomenon that fetal skin fibroblasts spontaneously transdifferentiated into keratinocyte-like cells in conventional culture, and evaluated the characteristics of KLCs and the potential mechanisms of the transdifferentiation process.Methods: HFF-1 were routinely cultured in ordinary DMEM medium for more than 40 days,and observed the cell morphology. The cytological properties of KLCs at the cellular and molecular levels were detected by RT-PCR, Western-blot, immunofluorescence, Transwell, and cell scratch experiments.The functionality and safety of KLCs were determined through wound healing and tumorigenicity experiments. And high-throughput transcriptome sequencing (RNA-seq) was performed to explore the mechanism underlying HFF-1 transdifferentiation.Results: The transdifferentiation process started on the 25th day and was completed by the 40th day. KLCs and KCs had similar expressions at the molecular and protein levels, both functioned similarly in wound healing and were non-tumorigenic.RNA-seq revealed that the transdifferentiation process was regulated by the activation of the classical Wnt/β-catenin signaling pathway, which could shorten the process to 10 days.Conclusion: This study demonstrates that HFF-1 can spontaneously transdifferentiate into KLCs with conventional culture conditions, and the Wnt/β-catenin signaling pathway regulates the transdifferentiation process.

scholarly journals Root extractive from Daphne genkwa benefits in wound healing of anal fistula through up-regulation of collagen genes in human skin fibroblasts

2017 ◽  
Vol 37 (2) ◽  
Author(s):  
Dong Yang ◽  
Jun-hua Xu ◽  
Ren-jie Shi
Keyword(s):  
Wound Healing ◽  
Human Skin ◽  
Anal Fistula ◽  
Healing Time ◽  
Skin Fibroblasts ◽  
Human Skin Fibroblasts ◽  
Protein Levels ◽  
Daphne Genkwa

Wound healing is the main problem in the therapy of anal fistula (AF). Daphne genkwa root has been traditionally used as an agent to soak sutures in operation of AF patients, but its function in wound healing remains largely unclear. The aim of the present study was to illuminate mechanisms of D. genkwa root treatment on AF. In the present study, 60 AF patients after surgery were randomly divided into two groups, external applied with or without the D. genkwa extractive. Wound healing times were compared and granulation tissues were collected. In vitro, we constructed damaged human skin fibroblasts (HSFs) with the treatment of TNF-α (10 μg/ml). Cell Count Kit-8 (CCK-8) and flow cytometry analysis were used to determine the effects of D. genkwa root extractive on cell viability, cell cycle and apoptosis of damaged HSFs. Furthermore, protein levels of TGF-β, COL1A1, COL3A1, Timp-1, matrix metalloproteinase (MMP)-3 (MMP-3) and MEK/ERK signalling pathways were investigated both in vivo and in vitro. Results showed that D. genkwa root extractive greatly shortens the wound healing time in AF patients. In granulation tissues and HSFs, treatment with the extractive significantly elevated the expressions of COL1A1, COL3A1, Timp-1, c-fos and Cyclin D1, while reduced the expression of MMP-3. Further detection presented that MEK/ERK signalling was activated after the stimulation of extractive in HSFs. Our study demonstrated that extractive from D. genkwa root could effectively improve wound healing in patients with AF via the up-regulation of fibroblast proliferation and expressions of COL1A1 and COL3A1.

scholarly journals Liraglutide Promotes Osteoblastic Differentiation in MC3T3-E1 Cells by ERK5 Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Yue Sun ◽  
Yuzhen Liang ◽  
Zhengming Li ◽  
Ning Xia
Keyword(s):  
Signaling Pathway ◽  
Osteoblastic Differentiation ◽  
Control Group ◽  
Activity Levels ◽  
Expression Levels ◽  
Protein Levels ◽  
Proliferation And Differentiation ◽  
Glucagon Like Peptide 1 ◽  
Differentiation And Proliferation

Liraglutide is a glucagon-like peptide-1 analogue widely used in the treatment of type 2 diabetes mellitus. However, the effects of liraglutide on osteoblast proliferation and differentiation in MC3T3-E1 cells have not been fully elucidated. In the present study, the promoting effects of liraglutide were investigated in MC3T3-E1 cells. The results indicated that cell viability was affected following the treatment of the cells with different concentrations of liraglutide (0, 10, 100, and 1000 nM) at different time periods of culture (24, 48, and 72 h). Moreover, the activity levels of alkaline phosphatase and the number of mineralized nodules in MC3T3-E1 cells were significantly increased following treatment with 100 nM liraglutide. The mRNA and protein levels of Col-1, OPG, and OCN in MC3T3-E1 cells were also markedly increased following 100 nM liraglutide treatment compared with those of the control group. The expression levels of the ERK5 signaling pathway key proteins (MEK5, p-ERK5, ERK5, and NUR77) were increased following liraglutide treatment in MC3T3-E1 cells, and the gene expression levels of the ERK5 signaling pathway were also elevated. Moreover, the ERK5 inhibitor XMD8-92 significantly decreased the expression levels of p-ERK5 and NUR77 as well as the proliferation of osteoblasts. However, these changes could be rescued by liraglutide to some extent. Therefore, these results revealed that liraglutide may promote osteoblastic differentiation and proliferation in MC3T3-E1 cells via the activation of the ERK5 signaling pathway.

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

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.

Scarless wound repair: a human fetal skin model

Development ◽  
1992 ◽  
Vol 114 (1) ◽  
pp. 253-259 ◽  
Author(s):  
H.P. Lorenz ◽  
M.T. Longaker ◽  
L.A. Perkocha ◽  
R.W. Jennings ◽  
M.R. Harrison ◽  
...  
Keyword(s):  
Wound Healing ◽  
Gestational Age ◽  
Animal Studies ◽  
Wound Repair ◽  
Mouse Skin ◽  
Skin Wound ◽  
Scar Formation ◽  
Fetal Skin ◽  
Skin Wound Healing ◽  
Thickness Skin

Animal studies demonstrate that the fetus heals cutaneous wounds by reformation of normal tissue architecture without scar formation. We have developed a new model to study human fetal skin wound healing. Grafts of human fetal skin placed onto athymic mice retain the morphologic features of normal development, although they differentiate at an accelerated rate when placed cutaneously compared to subcutaneously. Full-thickness skin grafts from human fetuses at 15 (n = 12), 17 (n = 11), 18 (n = 25), 19 (n = 20) and 22 (n = 13) weeks gestational age were placed onto athymic (nu/nu) mice in 2 locations: (1) cutaneously onto a fascial bed and thereby exposed to air or (2) subcutaneously in a pocket under the murine panniculus carnosus. Linear incisions were made in each graft 7 days after transplantation. Grafts were harvested at 7, 14 and 21 days postwounding and analyzed histologically for scar formation. By hematoxylin & eosin and Mallory's trichrome stains, complete epidermal and dermal graft wound healing without scar formation was demonstrated in the subcutaneous grafts at each gestational age studied. In contrast, scar was seen at all time points in the cutaneous grafts in both the incisional wound and at the interface of the fetal human skin graft and adult mouse skin, regardless of fetal skin gestational age.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Cellular and Molecular Characteristics of Scarless versus Fibrotic Wound Healing

2010 ◽  
Vol 2010 ◽  
pp. 1-11 ◽  
Author(s):  
Latha Satish ◽  
Sandeep Kathju
Keyword(s):  
Wound Healing ◽  
Wound Repair ◽  
Molecular Mechanisms ◽  
Skin Wound ◽  
Molecular Characteristics ◽  
Skin Wound Healing ◽  
Cellular Events ◽  
Compare And Contrast ◽  
Adult Skin ◽  
Fetal Wound

The purpose of this paper is to compare and contrast the discrete biology differentiating fetal wound repair from its adult counterpart. Integumentary wound healing in mammalian fetuses is essentially different from wound healing in adult skin. Adult (postnatal) skin wound healing is a complex and well-orchestrated process spurred by attendant inflammation that leads to wound closure with scar formation. In contrast, fetal wound repair occurs with minimal inflammation, faster re-epithelialization, and without the accumulation of scar. Although research into scarless healing began decades ago, the critical molecular mechanisms driving the process of regenerative fetal healing remain uncertain. Understanding the molecular and cellular events during regenerative healing may provide clues that one day enable us to modulate adult wound healing and consequently reduce scarring.

scholarly journals Wound healing: cellular mechanisms and pathological outcomes

Open Biology ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 200223 ◽  
Author(s):  
Holly N. Wilkinson ◽  
Matthew J. Hardman
Keyword(s):  
Wound Healing ◽  
Tissue Repair ◽  
Wound Repair ◽  
Complex Dynamic ◽  
Cellular Mechanisms ◽  
Cellular Events ◽  
High Prevalence ◽  
Healing Wounds ◽  
Socioeconomic Burden ◽  
Healing Impairment

Wound healing is a complex, dynamic process supported by a myriad of cellular events that must be tightly coordinated to efficiently repair damaged tissue. Derangement in wound-linked cellular behaviours, as occurs with diabetes and ageing, can lead to healing impairment and the formation of chronic, non-healing wounds. These wounds are a significant socioeconomic burden due to their high prevalence and recurrence. Thus, there is an urgent requirement for the improved biological and clinical understanding of the mechanisms that underpin wound repair. Here, we review the cellular basis of tissue repair and discuss how current and emerging understanding of wound pathology could inform future development of efficacious wound therapies.

Differential regulation of skin fibroblasts for their TGF-β1-dependent wound healing activities by biomimetic nanofibers

2016 ◽  
Vol 4 (31) ◽  
pp. 5246-5255 ◽  
Author(s):  
X. Fu ◽  
M. Xu ◽  
C. Jia ◽  
W. Xie ◽  
L. Wang ◽  
...  
Keyword(s):  
Wound Healing ◽  
Signaling Pathway ◽  
Differential Regulation ◽  
Skin Fibroblasts ◽  
Smad Signaling ◽  
Smad Signaling Pathway ◽  
Tgf Β1 ◽  
Biomimetic Nanofibers

Nanofibers with different compositions differentially regulate fibroblast phenotypes in a TGF-β1 rich milieu through the integrin-mediated TGF-β1/Smad signaling pathway.

scholarly journals Contractility, Transforming Growth Factor-β, and Plasmin in Fetal Skin Fibroblasts: Role in Scarless Wound Healing

1998 ◽  
Vol 43 (3) ◽  
pp. 403-409 ◽  
Author(s):  
Colleen Coleman ◽  
Tai-Lan Tuan ◽  
Sue Buckley ◽  
Kathryn D Anderson ◽  
David Warburton
Keyword(s):  
Wound Healing ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Skin Fibroblasts ◽  
Fetal Skin

scholarly journals GMP-Compliant Human Fetal Skin Fibroblasts for Wound Healing

2018 ◽  
Vol 5 (3) ◽  
Author(s):  
Parisa Goodarzi ◽  
Khadijeh Falahzadeh ◽  
Hamidreza Aghayan ◽  
Fereshteh Mohamadi Jahani ◽  
Moloud Payab ◽  
...  
Keyword(s):  
Wound Healing ◽  
Skin Fibroblasts ◽  
Fetal Skin

scholarly journals Regulatory Role of Nrf2 Signaling Pathway in Wound Healing Process

Molecules ◽  
2021 ◽  
Vol 26 (9) ◽  
pp. 2424
Author(s):  
Ipek Süntar ◽  
Sümeyra Çetinkaya ◽  
Emiliano Panieri ◽  
Sarmistha Saha ◽  
Brigitta Buttari ◽  
...  
Keyword(s):  
Wound Healing ◽  
Signaling Pathway ◽  
Bioactive Compounds ◽  
Wound Repair ◽  
Chronic Wounds ◽  
Healing Process ◽  
Wound Healing Process ◽  
Related Factor ◽  
Nrf2 Signaling Pathway

Wound healing involves a series of cellular events in damaged cells and tissues initiated with hemostasis and finally culminating with the formation of a fibrin clot. However, delay in the normal wound healing process during pathological conditions due to reactive oxygen species, inflammation and immune suppression at the wound site represents a medical challenge. So far, many therapeutic strategies have been developed to improve cellular homeostasis and chronic wounds in order to accelerate wound repair. In this context, the role of Nuclear factor erythroid 2-related factor 2 (Nrf2) during the wound healing process has been a stimulating research topic for therapeutic perspectives. Nrf2 is the main regulator of intracellular redox homeostasis. It increases cytoprotective gene expression and the antioxidant capacity of mammalian cells. It has been reported that some bioactive compounds attenuate cellular stress and thus accelerate cell proliferation, neovascularization and repair of damaged tissues by promoting Nrf2 activation. This review highlights the importance of the Nrf2 signaling pathway in wound healing strategies and the role of bioactive compounds that support wound repair through the modulation of this crucial transcription factor.

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