scholarly journals Suppression of α-catenin and adherens junctions enhances epithelial cell proliferation and motility via TACE-Mediated TGF-α autocrine/paracrine signaling

2020 ◽  
pp. mbc.E19-08-0474
Author(s):  
Eric N. Bunker ◽  
Graycen E. Wheeler ◽  
Douglas A. Chapnick ◽  
Xuedong Liu
Keyword(s):  
Cell Proliferation ◽  
Wound Healing ◽  
Cell Migration ◽  
Growth Factors ◽  
Adherens Junctions ◽  
Paracrine Signaling ◽  
Egfr Signaling ◽  
Exogenous Growth ◽  
Erk Activity ◽  
Exogenous Growth Factors

Sustained cell migration is essential for wound healing and cancer metastasis. The epidermal growth factor receptor (EGFR) signaling cascade is known to drive cell migration and proliferation. While the signal transduction downstream of EGFR has been extensively investigated, our knowledge of the initiation and maintenance of EGFR signaling during cell migration remains limited. The metalloprotease TACE is responsible for producing active EGFR family ligands in the via ligand shedding. Sustained TACE activity may perpetuate EGFR signaling and reduce a cell's reliance on exogenous growth factors. Using a cultured keratinocyte model system, we show that depletion of α-catenin perturbs adherens junctions, enhances cell proliferation and motility, and decreases dependence on exogenous growth factors. We show that the underlying mechanism for these observed phenotypical changes depends on enhanced autocrine/paracrine release of the EGFR ligand TGF-α in a TACE-dependent manner. We demonstrate that proliferating keratinocyte epithelial cell clusters display waves of oscillatory extracellular signal-regulated kinase (ERK) activity, which can be eliminated by TACE knockout, suggesting that these waves of oscillatory ERK activity depend on autocrine/paracrine signals produced by TACE. These results provide new insights into the regulatory role of adherens junctions in initiating and maintaining autocrine/paracrine signaling with relevance to wound healing and cellular transformation.

scholarly journals Local Regeneration of Dentin-Pulp Complex Using Controlled Release of FGF-2 and Naturally Derived Sponge-Like Scaffolds

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Chiaki Kitamura ◽  
Tatsuji Nishihara ◽  
Masamichi Terashita ◽  
Yasuhiko Tabata ◽  
Ayako Washio
Keyword(s):  
Wound Healing ◽  
Growth Factors ◽  
Controlled Release ◽  
Dental Pulp ◽  
Traumatic Injury ◽  
Pathological Changes ◽  
Irreversible Damage ◽  
Exogenous Growth ◽  
External Stimuli ◽  
Exogenous Growth Factors

Restorative and endodontic procedures have been recently developed in an attempt to preserve the vitality of dental pulp after exposure to external stimuli, such as caries infection or traumatic injury. When damage to dental pulp is reversible, pulp wound healing can proceed, whereas irreversible damage induces pathological changes in dental pulp, eventually requiring its removal. Nonvital teeth lose their defensive abilities and become severely damaged, resulting in extraction. Development of regeneration therapy for the dentin-pulp complex is important to overcome limitations with presently available therapies. Three strategies to regenerate the dentin-pulp complex have been proposed; regeneration of the entire tooth, local regeneration of the dentin-pulp complex from amputated dental pulp, and regeneration of dental pulp from apical dental pulp or periapical tissues. In this paper, we focus on the local regeneration of the dentin-pulp complex by application of exogenous growth factors and scaffolds to amputated dental pulp.

Apical Papilla Cells Are Capable of Forming a Pulplike Tissue with Odontoblastlike Cells without the Use of Exogenous Growth Factors

2018 ◽  
Vol 44 (11) ◽  
pp. 1671-1676 ◽  
Author(s):  
Cibele Pelissari ◽  
Adriana F.C. Paris ◽  
Andrea Mantesso ◽  
Marília Trierveiler
Keyword(s):  
Growth Factors ◽  
Exogenous Growth ◽  
Apical Papilla ◽  
Exogenous Growth Factors

scholarly journals The Antimicrobial Peptide Human β-Defensin-3 Accelerates Wound Healing by Promoting Angiogenesis, Cell Migration, and Proliferation Through the FGFR/JAK2/STAT3 Signaling Pathway

2021 ◽  
Vol 12 ◽  
Author(s):  
Miho Takahashi ◽  
Yoshie Umehara ◽  
Hainan Yue ◽  
Juan Valentin Trujillo-Paez ◽  
Ge Peng ◽  
...  
Keyword(s):  
Wound Healing ◽  
Cell Migration ◽  
Growth Factors ◽  
Growth Factor ◽  
Antimicrobial Peptide ◽  
Fibroblast Growth Factor ◽  
Human Fibroblasts ◽  
Janus Kinase ◽  
Fibroblast Growth ◽  
Angiogenic Growth Factors

In addition to its antimicrobial activity, the skin-derived antimicrobial peptide human β-defensin-3 (hBD-3) promotes keratinocyte proliferation and migration to initiate the wound healing process; however, its effects on fibroblasts, which are the major cell type responsible for wound healing, remain unclear. We investigated the role of hBD-3 in cell migration, proliferation and production of angiogenic growth factors in human fibroblasts and evaluated the in vivo effect of hBD-3 on promoting wound healing and angiogenesis. Following hBD-3 treatment, the mouse wounds healed faster and showed accumulation of neutrophils and macrophages in the early phase of wound healing and reduction of these phagocytes 4 days later. hBD-3-treated wounds also displayed an increased number of fibroblasts and newly formed vessels compared to those of the control mice. Furthermore, the expression of various angiogenic growth factors was increased in the hBD-3-treated wounds. Additionally, in vitro studies demonstrated that hBD-3 enhanced the secretion of angiogenic growth factors such as fibroblast growth factor, platelet-derived growth factor and vascular endothelial growth factor and induced the migration and proliferation of human fibroblasts. The hBD-3-mediated activation of fibroblasts involves the fibroblast growth factor receptor 1 (FGFR1)/Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) pathways, as evidenced by the inhibitory effects of pathway-specific inhibitors. We indeed confirmed that hBD-3 enhanced the phosphorylation of FGFR1, JAK2 and STAT3. Collectively, the current study provides novel evidence that hBD-3 might be a potential candidate for the treatment of wounds through its ability to promote wound healing, angiogenesis and fibroblast activation.

scholarly journals Abalone Collagen Extracts Potentiate Stem Cell Properties of Human Epidermal Keratinocytes

Marine Drugs ◽  
2019 ◽  
Vol 17 (7) ◽  
pp. 424
Author(s):  
Sajee Thaweekitphathanaphakdee ◽  
Pithi Chanvorachote ◽  
Sagaw Prateepchinda ◽  
Mattaka Khongkow ◽  
Apirada Sucontphunt
Keyword(s):  
Cell Proliferation ◽  
Wound Healing ◽  
Stem Cell ◽  
Cell Migration ◽  
Expression Level ◽  
Epidermal Keratinocytes ◽  
Stem Cell Markers ◽  
Spheroid Formation ◽  
Human Epidermal Keratinocytes ◽  
Cell Markers

Stem cell activities in human tissues are critical for tissue integrity and function. Maintaining keratinocyte stem cells (KSCs) stemness helps sustain healthy skin by supporting keratinocyte renewal, involving the formation of epidermal barriers. In this study, abalone collagen (AC) extracts with molecular weights of 3 kDa (AC 1) and 300 kDa (AC 2) were compared to the epidermal growth factor (EGF) for their effects on cell proliferation, cell migration (wound healing), spheroid formation, and the expression level of stem cell markers on human keratinocytes (HaCaT cells). Cell viability was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and cell proliferation was quantified by ATP and DNA content analysis and Sulforhodamine B (SRB) assays. Cell migration assay was determined using the scratch wound healing test. Spheroid formation was evaluated and the expression level of stem cell markers was investigated by western blot analysis. The results showed that AC 1 at the concentration of 100 µg/mL could stimulate HaCaT cell proliferation, migration, spheroid formation, and the expression level of stem cell markers (keratin 19, β-catenin, ALDH1A1) compared to the control. In conclusion, a smaller molecular weight of abalone collagen extract exhibits a better effect on keratinocytes proliferation, migration, and stemness, which could be a potential active ingredient in cosmeceutical products.

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