The Impairment of Wound Healing Process
is Correlated With Abnormalities of TNF-α
Production by Peritoneal Exudate Cells
in Obstructive Jaundiced Rats

The wound healing process and production of tumour necrosis factor alpha (TNF-α) by peritoneal cells of 7-day and 14-day obstructive jaundice (OJ) and sham-operated rats were investigated. In the study the skin wound breaking strength was measured, In addition such histological and biochemical parameters as fibroblast and endothelial cell proliferation, inflammatory cell infiltration and hydroxyproline content were evaluated in polyurethane sponge discs implanted subcutaneously into rats. TNF-α production by peritoneal exudate cells (PEC), both spontaneous and lipopolysaccharide (LPS)- induced was determined by a bioassay. In OJ rats the process of both early as well as late phase of healing was impaired. The breaking strength of skin wound was decreased, the fibroblast and endothelial cell proliferation and collagen deposition, as well as hydroxyproline content were diminished. In 7 day OJ the numbers of inflammatory cells in the implants were lowered with a subsequent slight increase on day 14 of OJ. The spontaneous and LPS induced TNF- α production by PEC were significantly higher in 7 day OJ as compared with sham-operated controls. On day 14 of OJ the LPS-induced TNF-α level was, in contrast, much lower and did not differ much from the spontaneous TNF-α production. We conclude that the impairment of wound healing in OJ results from disturbances in functioning of the immune system caused by systemic endotoxaemia.

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Systemic and topical administration of spermidine accelerates skin wound healing

10.21203/rs.3.rs-111107/v1 ◽

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.

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Systemic and topical administration of spermidine accelerates skin wound healing

Cell Communication and Signaling ◽

10.1186/s12964-021-00717-y ◽

2021 ◽

Vol 19 (1) ◽

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.

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Keratin Scaffolds Containing Casomorphin Stimulate Macrophage Infiltration and Accelerate Full-Thickness Cutaneous Wound Healing in Diabetic Mice

Molecules ◽

10.3390/molecules26092554 ◽

2021 ◽

Vol 26 (9) ◽

pp. 2554

Author(s):

Marek Konop ◽

Anna K. Laskowska ◽

Mateusz Rybka ◽

Ewa Kłodzińska ◽

Dorota Sulejczak ◽

...

Keyword(s):

Wound Healing ◽

Wound Dressing ◽

Healing Process ◽

Skin Wound ◽

Wound Healing Process ◽

Diabetic Mice ◽

Full Thickness ◽

Skin Wound Healing ◽

Impaired Wound Healing

Impaired wound healing is a major medical challenge, especially in diabetics. Over the centuries, the main goal of tissue engineering and regenerative medicine has been to invent biomaterials that accelerate the wound healing process. In this context, keratin-derived biomaterial is a promising candidate due to its biocompatibility and biodegradability. In this study, we evaluated an insoluble fraction of keratin containing casomorphin as a wound dressing in a full-thickness surgical skin wound model in mice (n = 20) with iatrogenically induced diabetes. Casomorphin, an opioid peptide with analgesic properties, was incorporated into keratin and shown to be slowly released from the dressing. An in vitro study showed that keratin-casomorphin dressing is biocompatible, non-toxic, and supports cell growth. In vivo experiments demonstrated that keratin-casomorphin dressing significantly (p < 0.05) accelerates the whole process of skin wound healing to the its final stage. Wounds covered with keratin-casomorphin dressing underwent reepithelization faster, ending up with a thicker epidermis than control wounds, as confirmed by histopathological and immunohistochemical examinations. This investigated dressing stimulated macrophages infiltration, which favors tissue remodeling and regeneration, unlike in the control wounds in which neutrophils predominated. Additionally, in dressed wounds, the number of microhemorrhages was significantly decreased (p < 0.05) as compared with control wounds. The dressing was naturally incorporated into regenerating tissue during the wound healing process. Applied keratin dressing favored reconstruction of more regular skin structure and assured better cosmetic outcome in terms of scar formation and appearance. Our results have shown that insoluble keratin wound dressing containing casomorphin supports skin wound healing in diabetic mice.

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A critical role of AREG for bleomycin-induced skin fibrosis

10.1101/2021.01.20.427509 ◽

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.

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Expression of VEGF and TGF-β Genes in Skin Wound Healing Process Induced Using Phenytoin in Male Rats

Jundishapur Journal of Health Sciences ◽

10.5812/jjhs.86041 ◽

2019 ◽

Vol In Press (In Press) ◽

Cited By ~ 2

Author(s):

Roghaye Savari ◽

Mohammad Shafiei ◽

Hamid Galehdari ◽

Mahnaz Kesmati

Keyword(s):

Wound Healing ◽

Healing Process ◽

Skin Wound ◽

Male Rats ◽

Wound Healing Process ◽

Skin Wound Healing

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P2Y2R activation by nucleotides promotes skin wound-healing process

Experimental Dermatology ◽

10.1111/exd.12440 ◽

2014 ◽

Vol 23 (7) ◽

pp. 480-485 ◽

Cited By ~ 26

Author(s):

Hana Jin ◽

Jihye Seo ◽

So Young Eun ◽

Young Nak Joo ◽

Sang Won Park ◽

...

Keyword(s):

Wound Healing ◽

Healing Process ◽

Skin Wound ◽

Wound Healing Process ◽

Skin Wound Healing

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A Disposable Photovoltaic Patch Controlling Cellular Microenvironment for Wound Healing

International Journal of Molecular Sciences ◽

10.3390/ijms19103025 ◽

2018 ◽

Vol 19 (10) ◽

pp. 3025 ◽

Cited By ~ 2

Author(s):

Hyeon-Ki Jang ◽

Jin Oh ◽

Gun-Jae Jeong ◽

Tae-Jin Lee ◽

Gwang-Bum Im ◽

...

Keyword(s):

Wound Healing ◽

Large Scale ◽

Healing Process ◽

Skin Wound ◽

Myoblast Differentiation ◽

Wound Healing Process ◽

Light Illumination ◽

Cellular Microenvironment ◽

Healing Processes

Electrical stimulation (ES) is known to affect the wound healing process by modulating skin cell behaviors. However, the conventional clinical devices that can generate ES for promoting wound healing require patient hospitalization due to large-scale of the extracorporeal devices. Herein, we introduce a disposable photovoltaic patch that can be applied to skin wound sites to control cellular microenvironment for promoting wound healing by generating ES. In vitro experiment results show that exogenous ES could enhance cell migration, proliferation, expression of extracellular matrix proteins, and myoblast differentiation of fibroblasts which are critical for wound healing. Our disposable photovoltaic patches were attached to the back of skin wound induced mice. Our patch successfully provided ES, generated by photovoltaic energy harvested from the organic solar cell under visible light illumination. In vivo experiment results show that the patch promoted cutaneous wound healing via enhanced host-inductive cell proliferation, cytokine secretion, and protein synthesis which is critical for wound healing process. Unlike the current treatments for wound healing that engage passive healing processes and often are unsuccessful, our wearable photovoltaic patch can stimulate regenerative activities of endogenous cells and actively contribute to the wound healing processes.

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The effect of earthworm extract on promoting skin wound healing

Bioscience Reports ◽

10.1042/bsr20171366 ◽

2018 ◽

Vol 38 (2) ◽

Cited By ~ 4

Author(s):

Zhen-han Deng ◽

Jian-jian Yin ◽

Wei Luo ◽

Ronak Naveenchandra Kotian ◽

Shan-shan Gao ◽

...

Keyword(s):

Wound Healing ◽

Healthcare System ◽

Transforming Growth Factor ◽

Healing Process ◽

White Blood Cells ◽

Skin Wound ◽

Wound Healing Process ◽

Blood Capillary ◽

Skin Wound Healing

Chronic nonhealing wounds pose a significant challenge to healthcare system because of its tremendous utilization of resources and time to heal. It has a well-deserved reputation for reducing the quality of life for those affected and represent a substantial economic burden to the healthcare system overall. Earthworms are used as a traditional Chinese medicine, and have been applied pharmacologically and clinically since a long time in China. However, there is paucity in data regarding its wound healing effects. Therefore, we investigated the effect of earthworm extract (EE) on skin wound healing process. The obtained data showed that EE has healing effects on local wound of mice. It decreased the wound healing time and reduced the ill-effects of inflammation as determined by macroscopic, histopathologic, hematologic, and immunohistochemistry parameters. The potential mechanism could be accelerated hydroxyproline and transforming growth factor-β secretion—thus increasing the synthesis of collagen, promoting blood capillary, and fibroblast proliferation. It could accelerate the removal of necrotic tissue and foreign bodies by speeding up the generation of interleukin-6, white blood cells, and platelets. It thus enhances immunity, reduces the risk of infection, and promotes wound healing. All in all, the obtained data demonstrated that EE improves quality of healing and could be used as a propitious wound healing agent.

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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 ◽

10.1186/s12915-019-0695-8 ◽

2019 ◽

Vol 17 (1) ◽

Cited By ~ 3

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.

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Immunohistological changes in skin wounds during the early periods of healing in a rat model

Veterinární Medicína ◽

10.17221/5253-vetmed ◽

2012 ◽

Vol 57 (No. 2) ◽

pp. 77-82 ◽

Cited By ~ 15

Author(s):

F. Sabol ◽

L. Dancakova ◽

P. Gal ◽

T. Vasilenko ◽

M. Novotny ◽

...

Keyword(s):

Wound Healing ◽

Wide Spectrum ◽

Smooth Muscle Actin ◽

Healing Process ◽

Skin Wound ◽

Hair Follicles ◽

In Vivo Model ◽

Wound Healing Process ◽

Rat Skin

The complexity of the wound healing process, which is still poorly understood, prompted us to perform an immunohistochemical investigation using rat skin as an in vivo model. Fifteen Sprague-Dawley rats were included in the experiment. Two round full thickness wounds, 4 mm in diameter, were made on the backs of all rats. Haematoxylin and eosin basic staining as well as antibodies against wide spectrum keratin, keratin 10, keratin 14, α-smooth muscle actin, vimentin, fibronectin, collagens Type 1 and 3, and the transcription factor Sox-2 were applied to paraffin and frozen sections of skin wound specimens two, six and fourteen days after surgery, respectively. New hair follicles with Sox-2-positive cells were present after fourteen days; keratin/vimentin positivity was restricted to specimens of day two. Collagen-3 expression prevailed over collagen-1 expression at all evaluated time intervals, except in the uninjured part of the dermis. In conclusion, rat skin wound healing is a dynamic process which can serve as a model for studying phenomena such as cell-cell interactions and transitions in vivo.

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