scholarly journals The Angiogenic Factor Cyr61 Activates a Genetic Program for Wound Healing in Human Skin Fibroblasts

2001 ◽  
Vol 276 (50) ◽  
pp. 47329-47337 ◽  
Author(s):  
Chih-Chiun Chen ◽  
Fan-E Mo ◽  
Lester F. Lau
Keyword(s):  
Gene Expression ◽  
Wound Healing ◽  
Wound Repair ◽  
Skin Fibroblasts ◽  
Matrix Remodeling ◽  
Cutaneous Wound Healing ◽  
Heparin Binding ◽  
Human Skin Fibroblasts ◽  
Cutaneous Wound

Cyr61 is a heparin-binding, extracellular matrix-associated protein of the CCN family, which also includes connective tissue growth factor, Nov, WISP-1, WISP-2, and WISP-3. Cyr61 is capable of multiple functions, including induction of angiogenesisin vivo. Purified Cyr61 mediates cell adhesion and induces adhesive signaling, stimulates cell migration, enhances cell proliferation, and promotes cell survival in both fibroblasts and endothelial cells. In this study, we have used cDNA array hybridization to identify genes regulated by Cyr61 in primary human skin fibroblasts. The Cyr61-regulated genes fall into several groups known to participate in processes important for cutaneous wound healing, including: 1) angiogenesis and lymphogenesis (VEGF-A and VEGF-C); 2) inflammation (interleukin-1β); 3) extracellular matrix remodeling (MMP1, MMP3, TIMP1, uPA, and PAI-1); and 4) cell-matrix interactions (Col1α1, Col1α2, and integrins α3and α5). Cyr61-mediated gene expression requires heparin binding activity of Cyr61, cellularde novotranscription, and protein synthesis and is largely dependent on the activation of p42/p44 MAPKs. Cyr61 regulates gene expression not only in serum-free medium but also in fibroblasts cultured on various matrix proteins or in the presence of 10% serum. These effects of Cyr61 can be sustained for at least 5 days, consistent with the time course of wound healingin vivo. Interestingly, Cyr61 can interact with transforming growth factor-β1 to regulate expression of specific genes in an antagonistic, additive, or synergistic manner. Furthermore, we show that theCyr61gene is highly induced in dermal fibroblasts of granulation tissue during cutaneous wound repair. Together, these results show thatCyr61is inducibly expressed in granulation tissues after wounding and that Cyr61 activates a genetic program for wound repair in skin fibroblasts. We propose a model in which Cyr61 integrates its activities on endothelial cells, fibroblasts, and macrophages to regulate the processes of angiogenesis, inflammation, and matrix remodeling in the context of cutaneous wound healing.

scholarly journals Microfluidic and Lab-on-a-Chip Systems for Cutaneous Wound Healing Studies

2021 ◽  
Author(s):  
Ghazal Shabestani Monfared ◽  
Peter Ertl ◽  
Mario Rothbauer
Keyword(s):  
Wound Healing ◽  
Molecular Mechanisms ◽  
Chronic Wounds ◽  
Cell Communication ◽  
Lab On A Chip ◽  
Tissue Level ◽  
Cutaneous Wound Healing ◽  
Cutaneous Wound

Cutaneous wound healing is a complex multi-stage process involving direct and indirect cell communication events with the aim of efficiently restoring the barrier function of the skin. One key aspect in cutaneous wound healing is associated with cell movement and migration into the physically, chemically and biologically injured area resulting in wound closure. Understanding the conditions under which cell migration is impaired and elucidating the cellular and molecular mechanisms that improve healing dynamics is therefore crucial in devising novel therapeutic strategies to elevate patient suffering, reduce scaring and eliminate chronic wounds. Following the global trend towards automation, miniaturization and integration of cell-based assays into microphysiological systems, conventional wound healing assays such as the scratch assay or cell exclusion assay have recently been translated and improved using microfluidics and lab-on-a-chip technologies. These miniaturized cell analysis systems allow precise spatial and temporal control over a range of dynamic microenvironmental factors including shear stress, biochemical and oxygen gradients to create more reliable in vitro models that resemble the in vivo microenvironment of a wound more closely on a molecular, cellular, and tissue level. The current review provides (a) an overview on the main molecular and cellular processes that take place during wound healing, (b) a brief introduction into conventional in vitro wound healing assays, and (c) a perspective on future cutaneous and vascular wound healing research using microfluidic technology.

Investigating Epidermal Interactions Through an In Vivo Cutaneous Wound-Healing Assay

2020 ◽  
pp. 1-11
Author(s):  
John L. Zemkewicz ◽  
Racheal G. Akwii ◽  
Constantinos M. Mikelis ◽  
Colleen L. Doçi
Keyword(s):  
Wound Healing ◽  
Cutaneous Wound Healing ◽  
Wound Healing Assay ◽  
Cutaneous Wound

In vivo evaluation of cutaneous wound healing activity of Mirabilis jalapa L radix

2013 ◽  
Vol 14 (2) ◽  
pp. 103-109 ◽  
Author(s):  
Jyotchna Gogoi ◽  
Khonamai Sewa Nakhuru ◽  
Pronobesh Chattophadhayay ◽  
Ashok Kumar Rai ◽  
Hemanta Kumar Gogoi ◽  
...  
Keyword(s):  
Wound Healing ◽  
Cutaneous Wound Healing ◽  
In Vivo Evaluation ◽  
Cutaneous Wound ◽  
Mirabilis Jalapa ◽  
Wound Healing Activity

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

Molecules ◽  
2019 ◽  
Vol 24 (8) ◽  
pp. 1595 ◽  
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.

Endothelial cell-derived small extracellular vesicles suppress cutaneous wound healing through regulating fibroblasts autophagy

2019 ◽  
Vol 133 (9) ◽  
Author(s):  
Tingting Zeng ◽  
Xiaoyi Wang ◽  
Wei Wang ◽  
Qiling Feng ◽  
Guojuan Lao ◽  
...  
Keyword(s):  
Wound Healing ◽  
Endothelial Cell ◽  
Extracellular Vesicles ◽  
Diabetic Foot ◽  
Collagen Synthesis ◽  
Foot Ulcer ◽  
Diabetic Foot Ulcer ◽  
Skin Fibroblasts ◽  
Cutaneous Wound Healing ◽  
Cutaneous Wound

Abstract Diabetic foot ulcer is a life-threatening clinical problem in diabetic patients. Endothelial cell-derived small extracellular vesicles (sEVs) are important mediators of intercellular communication in the pathogenesis of several diseases. However, the exact mechanisms of wound healing mediated by endothelial cell-derived sEVs remain unclear. sEVs were isolated from human umbilical vein endothelial cells (HUVECs) pretreated with or without advanced glycation end products (AGEs). The roles of HUVEC-derived sEVs on the biological characteristics of skin fibroblasts were investigated both in vitro and in vivo. We demonstrate that sEVs derived from AGEs-pretreated HUVECs (AGEs-sEVs) could inhibit collagen synthesis by activating autophagy of human skin fibroblasts. Additionally, treatment with AGEs-sEVs could delay the wound healing process in Sprague–Dawley (SD) rats. Further analysis indicated that miR-106b-5p was up-regulated in AGEs-sEVs and importantly, in exudate-derived sEVs from patients with diabetic foot ulcer. Consequently, sEV-mediated uptake of miR-106b-5p in recipient fibroblasts reduces expression of extracellular signal-regulated kinase 1/2 (ERK1/2), resulting in fibroblasts autophagy activation and subsequent collagen degradation. Collectively, our data demonstrate that miR-106b-5p could be enriched in AGEs-sEVs, then decreases collagen synthesis and delays cutaneous wound healing by triggering fibroblasts autophagy through reducing ERK1/2 expression.

scholarly journals Zebrafish as a Model System to Study the Mechanism of Cutaneous Wound Healing and Drug Discovery: Advantages and Challenges

2021 ◽  
Vol 14 (10) ◽  
pp. 1058
Author(s):  
Ruth Naomi ◽  
Hasnah Bahari ◽  
Muhammad Dain Yazid ◽  
Hashim Embong ◽  
Fezah Othman
Keyword(s):  
Wound Healing ◽  
Drug Discovery ◽  
Drug Formulation ◽  
New Drugs ◽  
Current Evidence ◽  
Cutaneous Wound Healing ◽  
Zebrafish Model ◽  
Signaling Mechanism ◽  
Cutaneous Wound

In humans, cutaneous wounds may heal without scars during embryogenesis. However, in the adult phase, the similar wound may undergo a few events such as homeostasis, blood clotting, inflammation, vascularization, and the formation of granulation tissue, which may leave a scar at the injury site. In consideration of this, research evolves daily to improve the healing mechanism in which the wound may heal without scarring. In regard to this, zebrafish (Danio rerio) serves as an ideal model to study the underlying signaling mechanism of wound healing. This is an important factor in determining a relevant drug formulation for wound healing. This review scrutinizes the biology of zebrafish and how this favors the cutaneous wound healing relevant to the in vivo evidence. This review aimed to provide the current insights on drug discovery for cutaneous wound healing based on the zebrafish model. The advantages and challenges in utilizing the zebrafish model for cutaneous wound healing are discussed in this review. This review is expected to provide an idea to formulate an appropriate drug for cutaneous wound healing relevant to the underlying signaling mechanism. Therefore, this narrative review recapitulates current evidence from in vivo studies on the cutaneous wound healing mechanism, which favours the discovery of new drugs. This article concludes with the need for zebrafish as an investigation model for biomedical research in the future to ensure that drug repositions are well suited for human skin.

scholarly journals Human bone marrow mesenchymal stem cells-derived exosomes stimulate cutaneous wound healing mediates through TGF-β/Smad signaling pathway

2020 ◽  
Author(s):  
Tiechao Jiang ◽  
Zhongyu Wang ◽  
Ji Sun
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Wound Healing ◽  
Mesenchymal Stem Cells ◽  
Cutaneous Wound Healing ◽  
Cutaneous Wound ◽  
Skin Cells ◽  
Smad Signaling Pathway ◽  
Marrow Mesenchymal Stem Cells

Abstract Background: Cutaneous wound healing represents a morphogenetic response to injury, and is designed to restore anatomic and physiological function. Human bone marrow mesenchymal stem cells-derived exosomes (hBM-MSCs-Ex) is a promising source for cell-free therapy and skin regeneration. Methods: In this study, we investigated the cell regeneration effects and its underlying mechanism of hBM-MSCs-Ex on cutaneous wound healing in rats. In vitro studies, we evaluated the role of hBM-MSCs-Ex in the two types of skin cells: human keratinocytes (HaCaT) and human dermal fibroblasts (HDFs) for the proliferation. For in vivo studies, we used a full-thickness skin wound model to evaluate the effects of hBM-MSCs-Ex on cutaneous wound healing in vivo. Results: The results demonstrated that hBM-MSCs-Ex promote both two types of skin cells growth effectively and accelerate the cutaneous wound healing. Interestingly, we found that hBM-MSCs-Ex significantly down-regulated TGF-β1, Smad2, Smad3, and Smad4 expression, while up-regulated TGF-β3 and Smad7 expression in the TGF-β/Smad signaling pathway. Conclusions: Our findings indicated that hBM-MSCs-Ex effectively promote the cutaneous wound healing through inhibiting the TGF-β/Smad signal pathway. The current results providing a new sight for the therapeutic strategy for the treatment of cutaneous wounds.

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