scholarly journals Hyaluronan-Phosphatidylethanolamine Polymers Form Pericellular Coats on Keratinocytes and Promote Basal Keratinocyte Proliferation

2014 ◽  
Vol 2014 ◽  
pp. 1-14 ◽  
Author(s):  
Caitlin J. Symonette ◽  
Aman Kaur Mann ◽  
Xiao Cherie Tan ◽  
Cornelia Tolg ◽  
Jenny Ma ◽  
...  
Keyword(s):  
Mouse Skin ◽  
Dermal Fibroblasts ◽  
Keratinocyte Differentiation ◽  
Detectable Effect ◽  
Aged Mouse ◽  
Keratinocyte Proliferation ◽  
Basal Keratinocyte ◽  
Cornified Layer ◽  
Topical Applications

Aged keratinocytes have diminished proliferative capacity and hyaluronan (HA) cell coats, which are losses that contribute to atrophic skin characterized by reduced barrier and repair functions. We formulated HA-phospholipid (phosphatidylethanolamine, HA-PE) polymers that form pericellular coats around cultured dermal fibroblasts independently of CD44 or RHAMM display. We investigated the ability of these HA-PE polymers to penetrate into aged mouse skin and restore epidermal function in vivo. Topically applied Alexa647-HA-PE penetrated into the epidermis and dermis, where it associated with both keratinocytes and fibroblasts. In contrast, Alexa647-HA was largely retained in the outer cornified layer of the epidermis and quantification of fluorescence confirmed that significantly more Alexa647-HA-PE penetrated into and was retained within the epidermis than Alexa647-HA. Multiple topical applications of HA-PE to shaved mouse skin significantly stimulated basal keratinocyte proliferation and epidermal thickness compared to HA or vehicle cream alone. HA-PE had no detectable effect on keratinocyte differentiation and did not promote local or systemic inflammation. These effects of HA-PE polymers are similar to those reported for endogenous epidermal HA in youthful skin and show that topical application of HA-PE polymers can restore some of the impaired functions of aged epidermis.

scholarly journals Adipose Tissue-Derived Mesenchymal Cells Support Skin Reepithelialization through Secretion of KGF-1 and PDGF-BB: Comparison with Dermal Fibroblasts

2012 ◽  
Vol 21 (11) ◽  
pp. 2441-2454 ◽  
Author(s):  
Vassilia-Ismini Alexaki ◽  
Despoina Simantiraki ◽  
Marianna Panayiotopoulou ◽  
Olga Rasouli ◽  
Maria Venihaki ◽  
...  
Keyword(s):  
Wound Healing ◽  
Adipose Tissue ◽  
Normal Skin ◽  
Human Adipose Tissue ◽  
Mesenchymal Cells ◽  
Dermal Fibroblasts ◽  
Skin Substitutes ◽  
Keratinocyte Proliferation

Epidermal organization and homeostasis are regulated by mesenchymal influences through paracrine actions. Until today, dermal fibroblasts (DFs) are used in the “dermal” layer to support keratinocyte growth in vitro in dermal and skin substitutes. In the present work, we used human adipose tissue-derived mesenchymal cells (ADMCs) as a support of keratinocyte growth in vitro (in monolayer culture and in 3D skin cell culture models) and in vivo (mouse wound healing models) and compared our findings with those obtained using dermal fibroblasts. ADMCs induce reepithelialization during wound healing more efficiently than DFs, by enhancing keratinocyte proliferation through cell cycle progression, and migration. This effect is mediated (at least partially) by a paracrine action of KGF-1 and PDGF-BB, which are more prominently expressed in ADMCs than in DFs. Furthermore, replacement of DFs by ADMCs in the dermal compartment of organotypic skin cultures leads to an artificial epidermis resembling to that of normal skin, concerning the general histology, although with a higher expression of cytokeratins 5 and 19. In Rag1 knockout mice, ADMCs induced a more rapid reepithelialization and a more effective wound healing, compared to dermal fibroblasts. In conclusion, we provide evidence that ADMCs can serve as supportive cells for primary keratinocyte cultures. In addition, because of their abundance and the great cell yield achieved during ADMC isolation, they represent an interesting cell source, with potential aspects for clinical use.

scholarly journals Transcription Factor Fli1 Regulates Collagen Fibrillogenesis in Mouse Skin

2008 ◽  
Vol 29 (2) ◽  
pp. 425-434 ◽  
Author(s):  
Yoshihide Asano ◽  
Margaret Markiewicz ◽  
Masahide Kubo ◽  
Gabor Szalai ◽  
Dennis K. Watson ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Transcriptional Activation ◽  
Molecular Mechanisms ◽  
Mrna Level ◽  
Mouse Skin ◽  
Dermal Fibroblasts ◽  
Acid Extraction ◽  
Fibrillar Collagen ◽  
Cultured Fibroblasts

ABSTRACT Biosynthesis of fibrillar collagen in the skin is precisely regulated to maintain proper tissue homeostasis; however, the molecular mechanisms involved in this process remain largely unknown. Transcription factor Fli1 has been shown to repress collagen synthesis in cultured dermal fibroblasts. This study investigated the role of Fli1 in regulation of collagen biosynthesis in mice skin in vivo using mice with the homozygous deletion of the C-terminal transcriptional activation (CTA) domain of the Fli1 gene (Fli1ΔCTA/ΔCTA). Skin analyses of the Fli1 mutant mice revealed a significant upregulation of fibrillar collagen genes at mRNA level, as well as increased collagen content as measured by acetic acid extraction and hydroxyproline assays. In addition, collagen fibrils contained ultrastructural abnormalities including immature thin fibrils and very thick irregularly shaped fibrils, which correlated with the reduced levels of decorin, fibromodulin, and lumican. Fibroblasts cultured from the skin of Fli1ΔCTA/ΔCTA mice maintained elevated synthesis of collagen mRNA and protein. Additional experiments in cultured fibroblasts have revealed that although Fli1 ΔCTA retains the ability to bind to the collagen promoter in vitro and in vivo, it no longer functions as transcriptional repressor. Together, these results establish Fli1 as a key regulator of the collagen homeostasis in the skin in vivo.

MITOCHONDRIA-TARGETED HYDROGEN SULFIDE DELIVERY MOLECULES PROTECT AGAINST UVA-INDUCED PHOTOAGING IN DERMAL FIBROBLASTS, AND IN MOUSE SKIN IN VIVO

2021 ◽  
Author(s):  
Jinapath Lohakul ◽  
Saowanee Jeayeng ◽  
Anyamanee Chaiprasongsuk ◽  
Roberta Torregrossa ◽  
Mark Wood ◽  
...  
Keyword(s):  
Hydrogen Sulfide ◽  
Mouse Skin ◽  
Dermal Fibroblasts

scholarly journals The Canine Papillomavirus E5 Protein Signals from the Endoplasmic Reticulum

2009 ◽  
Vol 83 (24) ◽  
pp. 12833-12841 ◽  
Author(s):  
Rachel Condjella ◽  
Xuefeng Liu ◽  
Frank Suprynowicz ◽  
Hang Yuan ◽  
Sawali Sudarshan ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Growth Inhibition ◽  
Er Stress ◽  
Protein A ◽  
Keratinocyte Differentiation ◽  
Keratinocyte Proliferation ◽  
Reading Frame ◽  
E5 Protein

ABSTRACT The recently discovered Canis familiaris papillomavirus (PV) type 2 (CfPV2) provides a unique opportunity to study PV gene functions in vitro and in vivo. Unlike the previously characterized canine oral PV, CfPV2 contains an E5 open reading frame and is associated with progression to squamous cell carcinoma. In the current study, we have expressed and characterized the CfPV2-encoded E5 protein, a small, hydrophobic, 41-amino-acid polypeptide. We demonstrate that, similar to the E5 protein from high-risk human PV type 16, the CfPV2 E5 protein is localized in the endoplasmic reticulum (ER) and that its expression decreases keratinocyte proliferation and cell life span. E5 expression also increases the percentage of cells in the G1 phase of the cell cycle, with a concomitant decrease in the percentage of cells in S phase. To identify a potential mechanism for E5-mediated growth inhibition from the ER, we developed a real-time PCR method to quantify the splicing of XBP1 mRNA as a measure of ER stress. We found that the CfPV2 E5 protein induced ER stress and that this, as well as the observed growth inhibition, is tempered significantly by coexpression of the CfPV2 E6 and E7 genes. It is possible that the spatial/temporal regulation of E6/E7 gene expression during keratinocyte differentiation might therefore modulate E5 activity and ER stress.

scholarly journals Human acellular amniotic membrane incorporating exosomes from adipose-derived mesenchymal stem cells promotes diabetic wound healing

2021 ◽  
Author(s):  
Shune Xiao ◽  
Chunfang Xiao ◽  
Yong Miao ◽  
Jin Wang ◽  
Ruosi Chen ◽  
...  
Keyword(s):  
Wound Healing ◽  
Amniotic Membrane ◽  
Mouse Skin ◽  
Skin Wound ◽  
Dermal Fibroblasts ◽  
Diabetic Wound ◽  
Wound Model ◽  
Diabetic Wound Healing

Abstract Background: Diabetic wounds threaten the health and quality of life of patients and their treatment remains challenging. ADSC-derived exosomes have shown encouraging results in enhancing diabetic wound healing. However, the common method of exosome administration is subcutaneous injection at several sites around the wound, causing further damage and preventing direct contact between the exosomes and the injury site. Methods: A diabetic mouse skin wound model was established. ADSC-derived exosomes (ADSC-Exos) were isolated and in vitro application of exosomes was evaluated using human umbilical vein endothelial cells (HUVECs) and human dermal fibroblasts (HDFs). After preparation and characterization of a scaffold of human acellular amniotic membrane (hAAM) loaded with ADSC-Exos in vitro , they were transplanted into wounds in vivo and wound healing phenomena were observed by histological and immunohistochemical analyses to identify the wound healing mechanism of the exosome-hAAM composites. Results: The hAAM scaffold dressing was very suitable for the delivery of exosomes. ADSC-Exos enhanced the proliferation and migration of HDFs and promoted proliferation and tube formation of HUVECs in vitro . In vivo results from a diabetic skin wound model showed that the hAAM-Exos dressing accelerated wound healing by regulating inflammation, stimulating vascularization and promoting the production of extracellular matrix. Conclusion: Exosome-incorporated hAAM scaffolds showed great potential in promoting diabetic skin wound healing, while also providing strong evidence for the future clinical applications of ADSC-derived exosomes.

scholarly journals The Human Papillomavirus Type 8 E2 Protein Suppresses β4-Integrin Expression in Primary Human Keratinocytes

2004 ◽  
Vol 78 (19) ◽  
pp. 10738-10746 ◽  
Author(s):  
Monika Oldak ◽  
Hans Smola ◽  
Monique Aumailley ◽  
Francisco Rivero ◽  
Herbert Pfister ◽  
...  
Keyword(s):  
Human Papillomaviruses ◽  
Keratinocyte Differentiation ◽  
Integrin Expression ◽  
Primary Human Keratinocytes ◽  
Down Regulation ◽  
Keratinocyte Proliferation ◽  
The Impact ◽  
Β4 Integrin ◽  
Stratified Epithelia

ABSTRACT Human papillomaviruses (HPVs) infect keratinocytes of skin and mucosa. Homeostasis of these constantly renewing, stratified epithelia is maintained by balanced keratinocyte proliferation and terminal differentiation. Instructions from the extracellular matrix engaging integrins strongly regulate these keratinocyte functions. The papillomavirus life cycle parallels the differentiation program of stratified epithelia, and viral progeny is produced only in terminally differentiating keratinocytes. Whereas papillomavirus oncoproteins can inhibit keratinocyte differentiation, the viral transcription factor E2 seems to counterbalance the impact of oncoproteins. In this study we show that high expression of HPV type 8 (HPV8) E2 in cultured primary keratinocytes leads to strong down-regulation of β4-integrin expression levels, partial reduction of β1-integrin, and detachment of transfected keratinocytes from underlying structures. Unlike HPV18 E2-expressing keratinocytes, HPV8 E2 transfectants did not primarily undergo apoptosis. HPV8 E2 partially suppressed β4-integrin promoter activity by binding to a specific E2 binding site leading to displacement of at least one cellular DNA binding factor. To our knowledge, we show for the first time that specific E2 binding contributes to regulation of a cellular promoter. In vivo, decreased β4-integrin expression is associated with detachment of keratinocytes from the underlying basement membrane and their egress from the basal to suprabasal layers. In papillomavirus disease, β4-integrin down-regulation in keratinocytes with higher E2 expression may push virally infected cells into the transit-amplifying compartment and ensure their commitment to the differentiation process required for virus replication.

scholarly journals Human acellular amniotic membrane incorporating exosomes from adipose-derived mesenchymal stem cells promotes diabetic wound healing

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Shune Xiao ◽  
Chunfang Xiao ◽  
Yong Miao ◽  
Jin Wang ◽  
Ruosi Chen ◽  
...  
Keyword(s):  
Wound Healing ◽  
Amniotic Membrane ◽  
Mouse Skin ◽  
Skin Wound ◽  
Dermal Fibroblasts ◽  
Diabetic Wound ◽  
Wound Model ◽  
Diabetic Wound Healing

Abstract Background Diabetic wounds threaten the health and quality of life of patients and their treatment remains challenging. ADSC-derived exosomes have shown encouraging results in enhancing diabetic wound healing. However, how to use exosomes in wound treatment effectively is a problem that needs to be addressed at present. Methods A diabetic mouse skin wound model was established. ADSC-derived exosomes (ADSC-Exos) were isolated, and in vitro application of exosomes was evaluated using human umbilical vein endothelial cells (HUVECs) and human dermal fibroblasts (HDFs). After preparation and characterization of a scaffold of human acellular amniotic membrane (hAAM) loaded with ADSC-Exos in vitro, they were transplanted into wounds in vivo and wound healing phenomena were observed by histological and immunohistochemical analyses to identify the wound healing mechanism of the exosome-hAAM composites. Results The hAAM scaffold dressing was very suitable for the delivery of exosomes. ADSC-Exos enhanced the proliferation and migration of HDFs and promoted proliferation and tube formation of HUVECs in vitro. In vivo results from a diabetic skin wound model showed that the hAAM-Exos dressing accelerated wound healing by regulating inflammation, stimulating vascularization, and promoting the production of extracellular matrix. Conclusion Exosome-incorporated hAAM scaffolds showed great potential in promoting diabetic skin wound healing, while also providing strong evidence for the future clinical applications of ADSC-derived exosomes.

scholarly journals Epidermal YAP2-5SA-ΔC Drives β-Catenin Activation to Promote Keratinocyte Proliferation in Mouse Skin In Vivo

2017 ◽  
Vol 137 (3) ◽  
pp. 716-726 ◽  
Author(s):  
Bassem Akladios ◽  
Veronica Mendoza-Reinoso ◽  
Michael S. Samuel ◽  
Edna C. Hardeman ◽  
Kiarash Khosrotehrani ◽  
...  
Keyword(s):  
Mouse Skin ◽  
Keratinocyte Proliferation

scholarly journals 1,2-Bis[(3-Methoxyphenyl)Methyl]Ethane-1,2-Dicarboxylic Acid Reduces UVB-Induced Photodamage In Vitro and In Vivo

Antioxidants ◽  
2019 ◽  
Vol 8 (10) ◽  
pp. 452 ◽  
Author(s):  
Wu ◽  
Lin ◽  
Hou ◽  
Chang ◽  
Wen ◽  
...  
Keyword(s):  
Protein Expression ◽  
Dicarboxylic Acid ◽  
Map Kinases ◽  
Mouse Skin ◽  
Dermal Fibroblasts ◽  
Premature Aging ◽  
Activator Protein 1 ◽  
Anti Inflammatory

This study investigated the effects and mechanisms of 1,2-bis[(3-methoxyphenyl)methyl]ethane-1,2-dicarboxylic acid (S4), a sesamin derivative, on anti-inflammation and antiphotoaging in vitro and in vivo. Human skin fibroblasts were treated with S4 and did not show cytotoxicity under concentrations of 5–50 µM. In addition, S4 also reduced ultraviolet (UV)B-induced intracellular reactive oxygen species (ROS) production. Additionally, S4 inhibited UVB-induced phosphorylation of mitogen-activated protein (MAP) kinases, activator protein-1 (AP-1), and matrix metalloproteinases (MMPs) overexpression. Furthermore, S4 also inhibited UVB-induced Smad7 protein expression and elevated total collagen content in human dermal fibroblasts. For anti-inflammatory activity, S4 inhibited UVB-induced nitric oxide synthase (i-NOS) and cyclooxygenase (COX)-2 protein expression and inhibited nuclear factor-kappaB (NF-ĸB) translocation into the nucleus. S4 ameliorated UVB-induced erythema and wrinkle formation in hairless mice. On histological observation, S4 also ameliorated UVB-induced epidermal hyperplasia and collagen degradation. S4 reduced UVB-induced MMP-1, interleukin (IL)-6, and NF-ĸB expression in the mouse skin. The results indicated that S4 had antiphotoaging and anti-inflammatory activities, protecting skin from premature aging.

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