scholarly journals A critical role of AREG for bleomycin-induced skin fibrosis

2021 ◽  
Author(s):  
Mary Yinghua Zhang ◽  
Shuyi Fang ◽  
Hongyu Gao ◽  
Xiaoli Zhang ◽  
Dongsheng Gu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Wound Healing ◽  
Oral Mucosa ◽  
Healing Process ◽  
Critical Role ◽  
Skin Fibrosis ◽  
Wound Healing Process ◽  
Organ Function ◽  
Signaling Axis

ABSTRACTWe report our discovery of an important player in the development of skin fibrosis, a hallmark of scleroderma. Scleroderma is a fibrotic disease, affecting 70,000 to 150,000 Americans. Fibrosis is a pathological wound healing process that produces an excessive extracellular matrix to interfere with normal organ function. Fibrosis contributes to nearly half of human mortality. Scleroderma has heterogeneous phenotypes, unpredictable outcomes, no validated biomarkers, and no effective treatment. Thus, strategies to slow down scleroderma progression represent an urgent medical need. While a pathological wound healing process like fibrosis leaves scars and weakens organ function, oral mucosa wound healing is a scarless process. After re-analyses of gene expression datasets from oral mucosa wound healing and skin fibrosis, we discovered that several pathways constitutively activated in skin fibrosis are transiently induced during oral mucosa wound healing process, particularly the amphiregulin (Areg) gene. Areg expression is upregulated ~10 folds 24hrs after oral mucosa wound but reduced to the basal level 3 days later. During bleomycin-induced skin fibrosis, a commonly used mouse model for skin fibrosis, Areg is up-regulated throughout the fibrogenesis and is associated with elevated cell proliferation in the dermis. To demonstrate the role of Areg for skin fibrosis, we used mice with Areg knockout, and found that Areg deficiency essentially prevents bleomycin-induced skin fibrosis. We further determined that bleomycin-induced cell proliferation in the dermis was not observed in the Areg null mice. Furthermore, we found that inhibiting MEK, a downstream signaling effector of Areg, by selumetinib also effectively blocked bleomycin-based skin fibrosis model. Based on these results, we concluded that the Areg-EGFR-MEK signaling axis is critical for skin fibrosis development. Blocking this signaling axis may be effective in treating scleroderma.

scholarly journals A critical role of AREG for bleomycin-induced skin fibrosis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mary Yinghua Zhang ◽  
Shuyi Fang ◽  
Hongyu Gao ◽  
Xiaoli Zhang ◽  
Dongsheng Gu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Wound Healing ◽  
Oral Mucosa ◽  
Healing Process ◽  
Critical Role ◽  
Skin Fibrosis ◽  
Wound Healing Process ◽  
Organ Function ◽  
Signaling Axis

AbstractWe report our discovery of an important player in the development of skin fibrosis, a hallmark of scleroderma. Scleroderma is a fibrotic disease, affecting 70,000 to 150,000 Americans. Fibrosis is a pathological wound healing process that produces an excessive extracellular matrix to interfere with normal organ function. Fibrosis contributes to nearly half of human mortality. Scleroderma has heterogeneous phenotypes, unpredictable outcomes, no validated biomarkers, and no effective treatment. Thus, strategies to slow down scleroderma progression represent an urgent medical need. While a pathological wound healing process like fibrosis leaves scars and weakens organ function, oral mucosa wound healing is a scarless process. After re-analyses of gene expression datasets from oral mucosa wound healing and skin fibrosis, we discovered that several pathways constitutively activated in skin fibrosis are transiently induced during oral mucosa wound healing process, particularly the amphiregulin (Areg) gene. Areg expression is upregulated ~ 10 folds 24hrs after oral mucosa wound but reduced to the basal level 3 days later. During bleomycin-induced skin fibrosis, a commonly used mouse model for skin fibrosis, Areg is up-regulated throughout the fibrogenesis and is associated with elevated cell proliferation in the dermis. To demonstrate the role of Areg for skin fibrosis, we used mice with Areg knockout, and found that Areg deficiency essentially prevents bleomycin-induced skin fibrosis. We further determined that bleomycin-induced cell proliferation in the dermis was not observed in the Areg null mice. Furthermore, we found that inhibiting MEK, a downstream signaling effector of Areg, by selumetinib also effectively blocked bleomycin-based skin fibrosis model. Based on these results, we concluded that the Areg-EGFR-MEK signaling axis is critical for skin fibrosis development. Blocking this signaling axis may be effective in treating scleroderma.

scholarly journals A critical role of AREG for bleomycin-induced skin fibrosis

2021 ◽  
Author(s):  
Mary Yinghua zhang ◽  
Shuyi Fang ◽  
Hongyu Gao ◽  
xiaoli zhang ◽  
Dongsheng Gu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Wound Healing ◽  
Oral Mucosa ◽  
Healing Process ◽  
Critical Role ◽  
Skin Fibrosis ◽  
Wound Healing Process ◽  
Organ Function ◽  
Signaling Axis

Abstract We report our discovery of an important player in the development of skin fibrosis, a hallmark of scleroderma. Scleroderma is a fibrotic disease, affecting 70,000 to 150,000 Americans. Fibrosis is a pathological wound healing process that produces an excessive extracellular matrix to interfere with normal organ function. Fibrosis contributes to nearly half of human mortality. Scleroderma has heterogeneous phenotypes, unpredictable outcomes, no validated biomarkers, and no effective treatment. Thus, strategies to slow down scleroderma progression represent an urgent medical need. While a pathological wound healing process like fibrosis leaves scars and weakens organ function, oral mucosa wound healing is a scarless process. After re-analyses of gene expression datasets from oral mucosa wound healing and skin fibrosis, we discovered that several pathways constitutively activated in skin fibrosis are transiently induced during oral mucosa wound healing process, particularly the amphiregulin (Areg) gene. Areg expression is upregulated ~ 10 folds 24hrs after oral mucosa wound but reduced to the basal level 3 days later. During bleomycin-induced skin fibrosis, a commonly used mouse model for skin fibrosis, Areg is up-regulated throughout the fibrogenesis and is associated with elevated cell proliferation in the dermis. To demonstrate the role of Areg for skin fibrosis, we used mice with Areg knockout, and found that Areg deficiency essentially prevents bleomycin-induced skin fibrosis. We further determined that bleomycin-induced cell proliferation in the dermis was not observed in the Areg null mice. Furthermore, we found that inhibiting MEK, a downstream signaling effector of Areg, by selumetinib also effectively blocked bleomycin-based skin fibrosis model. Based on these results, we concluded that the Areg-EGFR-MEK signaling axis is critical for skin fibrosis development. Blocking this signaling axis may be effective in treating scleroderma.

scholarly journals Site-Specific Expression Pattern of PIWI-Interacting RNA in Skin and Oral Mucosal Wound Healing

2020 ◽  
Vol 21 (2) ◽  
pp. 521
Author(s):  
Chen ◽  
Chen ◽  
Simões ◽  
Wu ◽  
Dai ◽  
...  
Keyword(s):  
Wound Healing ◽  
Oral Mucosa ◽  
Wound Repair ◽  
Healing Process ◽  
Wound Healing Process ◽  
Site Specific ◽  
Mucosal Epithelium ◽  
Tissue Specific ◽  
Mucosal Wound

The oral mucosa exhibits exceptional healing capability when compared to skin. Recent studies suggest that intrinsic differences in coding genes and regulatory small non-coding RNA (sncRNA) genes (e.g., microRNAs) may underlie the exceptional healing that occurs in the oral mucosa. Here, we investigate the role of a novel class of sncRNA—Piwi-interacting RNA (piRNA)—in the tissue-specific differential response to injury. An abundance of piRNAs was detected in both skin and oral mucosal epithelium during wound healing. The expression of PIWI genes (the obligate binding partners of piRNAs) was also detected in skin and oral wound healing. This data suggested that PIWI-piRNA machinery may serve an unknown function in the highly orchestrated wound healing process. Furthermore, unique tissue-specific piRNA profiles were obtained in the skin and oral mucosal epithelium, and substantially more changes in piRNA expression were observed during skin wound healing than oral mucosal wound healing. Thus, we present the first clue suggesting a role of piRNA in wound healing, and provide the first site-specific piRNA profile of skin and oral mucosal wound healing. These results serve as a foundation for the future investigation of the functional contribution(s) of piRNA in wound repair and tissue regeneration.

Chondroitin Sulfate in Palatal Wound Healing

2004 ◽  
Vol 83 (11) ◽  
pp. 880-885 ◽  
Author(s):  
X.H. Zou ◽  
W.C. Foong ◽  
T. Cao ◽  
B.H. Bay ◽  
H.W. Ouyang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Wound Healing ◽  
Cell Adhesion ◽  
Chondroitin Sulfate ◽  
Healing Process ◽  
Wound Healing Process ◽  
Dose Dependent Increase ◽  
Dose Dependent

Chondroitin sulfate is up-regulated in granulation tissue during wound healing. To investigate the role of chondroitin sulfate in the wound-healing process after surgical repair of cleft palate, we isolated and cultured rabbit palatal fibroblasts. Treatment with chondroitin-6-sulfate resulted in a dose-dependent increase in cell adhesion and cell proliferation, whereas the reverse effects were seen after chondroitinase degradation of chondroitin sulfate. The biological actions of chondroitin sulfate appeared to be dependent on the presence and position of sulfate groups. Inhibition of glycosaminoglycan sulfation by chlorate treatment led to reduced cell adhesion and cell proliferation and a slower rate of wound closure in vitro. Furthermore, exposure to chondroitin-4-sulfate resulted in a dose-dependent reduction in cell adhesion. Together, these results show that chondroitin sulfate is involved in palatal wound healing.

scholarly journals Role of glyoxalases in wound healing process: an in vitro study

2021 ◽  
Vol 165 ◽  
pp. 39
Author(s):  
Francesca Lombardi ◽  
Silvano Santini ◽  
Paola Palumbo ◽  
Valeria Cordone ◽  
Virginio Bignotti ◽  
...  
Keyword(s):  
Wound Healing ◽  
Healing Process ◽  
In Vitro Study ◽  
Vitro Study ◽  
Wound Healing Process

scholarly journals Systemic and topical administration of spermidine accelerates skin wound healing

2020 ◽  
Author(s):  
Daisuke Ito ◽  
Hiroyasu Ito ◽  
Takayasu Ideta ◽  
Ayumu Kanbe ◽  
Soranobu Ninomiya ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Wound Healing ◽  
Wound Repair ◽  
Healing Process ◽  
Topical Administration ◽  
Skin Wound ◽  
Wound Healing Process ◽  
Skin Wound Healing

Abstract Background The skin wound healing process is regulated by various cytokines, chemokines, and growth factors. Recent reports have demonstrated that spermine/spermidine (SPD) promote wound healing through urokinase-type plasminogen activator (uPA)/uPA receptor (uPAR) signaling in vitro. Here, we investigated whether the systemic and topical administration of SPD would accelerate the skin wound-repair process in vivo.Methods A skin wound repair model was established using C57BL/6 J mice. SPD was mixed with white petrolatum for topical administration. For systemic administration, SPD mixed with drinking water was orally administered. Changes in wound size over time were calculated using digital photography.Results Systemic and topical SPD treatment significantly accelerated skin wound healing. The administration of SPD promoted the uPA/uPAR pathway in wound sites. Moreover, topical treatment with SPD enhanced the expression of IL-6 and TNF-α in wound sites. Scratch and cell proliferation assays revealed that SPD administration accelerated scratch wound closure and cell proliferation in vitro.Conclusion These results indicate that treatment with SPD promotes skin wound healing through activation of the uPA/uPAR pathway and induction of the inflammatory response in wound sites. The administration of SPD might contribute to new effective treatments to accelerate skin wound healing.

Acceleration of the healing process of full-thickness wounds using hydrophilic chitosan–silica hybrid sponge in a porcine model

2018 ◽  
Vol 32 (8) ◽  
pp. 1011-1023 ◽  
Author(s):  
Ji-Ung Park ◽  
Seol-Ha Jeong ◽  
Eun-Ho Song ◽  
Juha Song ◽  
Hyoun-Ee Kim ◽  
...  
Keyword(s):  
Wound Healing ◽  
Surface Characterization ◽  
Porcine Model ◽  
Healing Process ◽  
Synergetic Effect ◽  
Wound Healing Process ◽  
Cutaneous Wounds ◽  
Chemical Coupling

In this study, we evaluated the surface characterization of a novel chitosan–silica hybridized membrane and highlighted the substantial role of silica in the wound environment. The chemical coupling of chitosan and silica resulted in a more condensed network compared with pure chitosan, which was eventually able to stably maintain its framework, particularly in the wet state. In addition, we closely observed the wound-healing process along with the surface interaction between chitosan–silica and the wound site using large-surface-area wounds in a porcine model. Our evidence indicates that chitosan–silica exerts a synergetic effect of both materials to promote a remarkable wound-healing process. In particular, the silica in chitosan–silica accelerated wound closure including wound contraction, and re-epithelialization via enhancement of cell recruitment, epidermal maturity, neovascularization, and granulation tissue formation compared with pure chitosan and other commercial dressing materials. This advanced wound dressing material may lead to effective treatment for problematic cutaneous wounds and can be further applied for human skin regeneration.

scholarly journals Regeneration in the ctenophore Mnemiopsis leidyi occurs in the absence of a blastema, requires cell division, and is temporally separable from wound healing

BMC Biology ◽  
2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Julia Ramon-Mateu ◽  
S. Tori Ellison ◽  
Thomas E. Angelini ◽  
Mark Q. Martindale
Keyword(s):  
Cell Proliferation ◽  
Wound Healing ◽  
Healing Process ◽  
Whole Body ◽  
Local Source ◽  
Mnemiopsis Leidyi ◽  
Wound Healing Process ◽  
Marine Animals ◽  
High Fecundity ◽  
Ability To Regenerate

Abstract Background The ability to regenerate is a widely distributed but highly variable trait among metazoans. A variety of modes of regeneration has been described for different organisms; however, many questions regarding the origin and evolution of these strategies remain unanswered. Most species of ctenophore (or “comb jellies”), a clade of marine animals that branch off at the base of the animal tree of life, possess an outstanding capacity to regenerate. However, the cellular and molecular mechanisms underlying this ability are unknown. We have used the ctenophore Mnemiopsis leidyi as a system to study wound healing and adult regeneration and provide some first-time insights of the cellular mechanisms involved in the regeneration of one of the most ancient extant group of multicellular animals. Results We show that cell proliferation is activated at the wound site and is indispensable for whole-body regeneration. Wound healing occurs normally in the absence of cell proliferation forming a scar-less wound epithelium. No blastema-like structure is generated at the cut site, and pulse-chase experiments and surgical intervention show that cells originating in the main regions of cell proliferation (the tentacle bulbs) do not seem to contribute to the formation of new structures after surgical challenge, suggesting a local source of cells during regeneration. While exposure to cell-proliferation blocking treatment inhibits regeneration, the ability to regenerate is recovered when the treatment ends (days after the original cut), suggesting that ctenophore regenerative capabilities are constantly ready to be triggered and they are somehow separable of the wound healing process. Conclusions Ctenophore regeneration takes place through a process of cell proliferation-dependent non-blastemal-like regeneration and is temporally separable of the wound healing process. We propose that undifferentiated cells assume the correct location of missing structures and differentiate in place. The remarkable ability to replace missing tissue, the many favorable experimental features (e.g., optical clarity, high fecundity, rapid regenerative performance, stereotyped cell lineage, sequenced genome), and the early branching phylogenetic position in the animal tree, all point to the emergence of ctenophores as a new model system to study the evolution of animal regeneration.

scholarly journals Regeneration in the absence of a blastema requires cell division but is not tied to wound healing in the ctenophore Mnemiopsis leidyi

2019 ◽  
Author(s):  
Julia Ramon-Mateu ◽  
Tori Ellison ◽  
Thomas E. Angelini ◽  
Mark Q. Martindale
Keyword(s):  
Cell Proliferation ◽  
Wound Healing ◽  
Healing Process ◽  
Whole Body ◽  
Local Source ◽  
Mnemiopsis Leidyi ◽  
Wound Healing Process ◽  
Marine Animals ◽  
High Fecundity ◽  
Ability To Regenerate

ABSTRACTBackgroundThe ability to regenerate is a widely distributed but highly variable trait among metazoans. A variety of modes of regeneration has been described for different organisms, however, many questions regarding the origin and evolution of these strategies remain unanswered. Most species of ctenophore (or “comb jellies”), a clade of marine animals that branch off at the base of the animal tree of life, possess an outstanding capacity to regenerate. However, the cellular and molecular mechanisms underlying this ability are unknown. We have used the ctenophore Mnemiopsis leidyi as a system to study wound healing and adult regeneration and provide some first-time insights of the cellular mechanisms involved in the regeneration of one of the most ancient extant group of multicellular animals.ResultsWe show that cell proliferation is activated at the wound site and is indispensable for whole-body regeneration. Wound healing occurs normally in the absence of cell proliferation forming a scar-less wound epithelium. No blastema-like structure is generated at the cut site, rather undifferentiated cells assume the correct location of missing structures and differentiate in place. Pulse-chase experiments and surgical intervention show that cells originating in the main regions of cell proliferation (the tentacle bulbs) do not seem to contribute to the formation of new structures after surgical challenge, suggesting a local source of cells during regeneration. While exposure to cell-proliferation blocking treatment inhibits regeneration, the ability to regenerate is recovered when the treatment ends (days after the original cut), suggesting that ctenophore regenerative capabilities are constantly ready to be triggered and they are somehow separable of the wound healing process.ConclusionsCtenophore regeneration takes place through a process of cell proliferation-dependent non blastemal-like regeneration and is temporally separable of the wound healing process. The remarkable ability to replace missing tissue, the many favorable experimental features (e.g. optical clarity, high fecundity, rapid regenerative performance, stereotyped cell lineage, sequenced genome), and the early branching phylogenetic position in the animal tree, all point to the emergence of ctenophores as a new model system to study the evolution of animal regeneration.

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