International Journal of Molecular Sciences

Research

12 pages, 1449 KiB

Open AccessArticle

The Remodeling of Dermal Collagen Fibrous Structures in Mice under Zero Gravity: The Role of Mast Cells

by Viktoriya Shishkina, Andrey Kostin, Artem Volodkin, Vera Samoilova, Igor Buchwalow, Markus Tiemann and Dmitri Atiakshin

Int. J. Mol. Sci. 2023, 24(3), 1939; https://doi.org/10.3390/ijms24031939 - 18 Jan 2023

Cited by 3 | Viewed by 2005

Abstract

Mechanisms of adaptive rearrangements of the fibrous extracellular matrix of connective tissues under microgravity practically remain unexplored, despite the most essential functions of the stroma existing to ensure the physiological activity of internal organs. Here we analyzed the biomaterial (the skin dermis) of [...] Read more.

Mechanisms of adaptive rearrangements of the fibrous extracellular matrix of connective tissues under microgravity practically remain unexplored, despite the most essential functions of the stroma existing to ensure the physiological activity of internal organs. Here we analyzed the biomaterial (the skin dermis) of C57BL/6J mice from the Rodent Research-4 experiment after a long stay in space flight. The biomaterial was fixed onboard the International Space Station. It was found that weightlessness resulted in a relative increase in type III collagen-rich fibers compared to other fibrous collagens in the skin. The number of mast cells in the skin did not change, but their secretory activity increased. At the same time, co-localization of mast cells with fibroblasts, as well as impregnated fibers, was reduced. Potential molecular–cellular causes of changes in the activity of fibrillogenesis under zero-gravity conditions and the slowdown of the polymerization of tropocollagen molecules into supramolecular fibrous structures, as well as a relative decrease in the number of fibrous structures with a predominant content of type-I collagen, are discussed. The data obtained evidence of the different sensitivity levels of the fibrous and cellular components of a specific tissue microenvironment of the skin to zero-gravity conditions. The obtained data should be taken into account in the systematic planning of long-term space missions in order to improve the prevention of undesirable effects of weightlessness. Full article

(This article belongs to the Special Issue Dermal Research: From Molecular Mechanisms to Pathology)

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12 pages, 3170 KiB

Open AccessArticle

ICOSL Stimulation by ICOS-Fc Accelerates Cutaneous Wound Healing In Vivo

by Ian Stoppa, Casimiro Luca Gigliotti, Nausicaa Clemente, Deepika Pantham, Chiara Dianzani, Chiara Monge, Chiara Puricelli, Roberta Rolla, Salvatore Sutti, Filippo Renò, Renzo Boldorini, Elena Boggio and Umberto Dianzani

Int. J. Mol. Sci. 2022, 23(13), 7363; https://doi.org/10.3390/ijms23137363 - 1 Jul 2022

Cited by 6 | Viewed by 1997

Abstract

Background: ICOS and its ligand ICOSL are immune receptors whose interaction triggers bidirectional signals that modulate the immune response and tissue repair. Aim: The aim of this study was to assess the in vivo effects of ICOSL triggering by ICOS-Fc, a recombinant soluble [...] Read more.

Background: ICOS and its ligand ICOSL are immune receptors whose interaction triggers bidirectional signals that modulate the immune response and tissue repair. Aim: The aim of this study was to assess the in vivo effects of ICOSL triggering by ICOS-Fc, a recombinant soluble form of ICOS, on skin wound healing. Methods: The effect of human ICOS-Fc on wound healing was assessed, in vitro, and, in vivo, by skin wound healing assay using ICOS^−/− and ICOSL^−/− knockout (KO) mice and NOD-SCID-IL2R null (NSG) mice. Results: We show that, in wild type mice, treatment with ICOS-Fc improves wound healing, promotes angiogenesis, preceded by upregulation of IL-6 and VEGF expression; increases the number of fibroblasts and T cells, whereas it reduces that of neutrophils; and increases the number of M2 vs. M1 macrophages. Fittingly, ICOS-Fc enhanced M2 macrophage migration, while it hampered that of M1 macrophages. ICOS^−/− and ICOSL^−/− KO, and NSG mice showed delayed wound healing, and treatment with ICOS-Fc improved wound closure in ICOS^−/− and NSG mice. Conclusion: These data show that the ICOS/ICOSL network cooperates in tissue repair, and that triggering of ICOSL by ICOS-Fc improves cutaneous wound healing by increasing angiogenesis and recruitment of reparative macrophages. Full article

(This article belongs to the Special Issue Dermal Research: From Molecular Mechanisms to Pathology)

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14 pages, 1931 KiB

Open AccessArticle

Photoaging and Sequential Function Reversal with Cellular-Resolution Optical Coherence Tomography in a Nude Mice Model

by Yen-Jen Wang, Chang-Cheng Chang, Meng-En Lu, Yu-Hung Wu, Jia-Wei Shen, Hsiu-Mei Chiang and Bor-Shyh Lin

Int. J. Mol. Sci. 2022, 23(13), 7009; https://doi.org/10.3390/ijms23137009 - 23 Jun 2022

Cited by 4 | Viewed by 2161

Abstract

Although nude mice are an ideal photoaging research model, skin biopsies result in inflammation and are rarely performed at baseline. Meanwhile, studies on antiphotoaging antioxidants or rejuvenation techniques often neglect the spontaneous reversal capacity. Full-field optical coherence tomography (FFOCT) can acquire cellular details [...] Read more.

Although nude mice are an ideal photoaging research model, skin biopsies result in inflammation and are rarely performed at baseline. Meanwhile, studies on antiphotoaging antioxidants or rejuvenation techniques often neglect the spontaneous reversal capacity. Full-field optical coherence tomography (FFOCT) can acquire cellular details noninvasively. This study aimed to establish a photoaging and sequential function reversal nude mice model assisted by an in vivo cellular resolution FFOCT system. We investigated whether a picosecond alexandrite laser (PAL) with a diffractive lens array (DLA) accelerated the reversal. In the sequential noninvasive assessment using FFOCT, a spectrophotometer, and DermaLab Combo^®, the photodamage percentage recovery plot demonstrated the spontaneous recovery capacity of the affected skin by UVB-induced transepidermal water loss and UVA-induced epidermis thickening. A PAL with DLA not only accelerated skin barrier regeneration with epidermal polarity, but also increased dermal neocollagenesis, whereas the nonlasered group still had >60% collagen intensity loss and 40% erythema from photodamage. Our study demonstrated that FFOCT images accurately resemble the living tissue. The photoaging and sequential function reversal model provides a reference to assess the spontaneous recovery capacity of nude mice from photodamage. This model can be utilized to evaluate the sequential noninvasive photodamage and reversal effects after other interventions. Full article

(This article belongs to the Special Issue Dermal Research: From Molecular Mechanisms to Pathology)

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14 pages, 6424 KiB

Open AccessArticle

Polymerizable Skin Hydrogel for Full Thickness Wound Healing

by Mairobi Persinal-Medina, Sara Llames, Manuel Chacón, Natalia Vázquez, Marta Pevida, Ignacio Alcalde, Sergio Alonso-Alonso, Laura María Martínez-López, Jesús Merayo-Lloves and Álvaro Meana

Int. J. Mol. Sci. 2022, 23(9), 4837; https://doi.org/10.3390/ijms23094837 - 27 Apr 2022

Cited by 9 | Viewed by 2538

Abstract

The skin is the largest organ in the human body, comprising the main barrier against the environment. When the skin loses its integrity, it is critical to replace it to prevent water loss and the proliferation of opportunistic infections. For more than 40 [...] Read more.

The skin is the largest organ in the human body, comprising the main barrier against the environment. When the skin loses its integrity, it is critical to replace it to prevent water loss and the proliferation of opportunistic infections. For more than 40 years, tissue-engineered skin grafts have been based on the in vitro culture of keratinocytes over different scaffolds, requiring between 3 to 4 weeks of tissue culture before being used clinically. In this study, we describe the development of a polymerizable skin hydrogel consisting of keratinocytes and fibroblast entrapped within a fibrin scaffold. We histologically characterized the construct and evaluated its use on an in vivo wound healing model of skin damage. Our results indicate that the proposed methodology can be used to effectively regenerate skin wounds, avoiding the secondary in vitro culture steps and thus, shortening the time needed until transplantation in comparison with other bilayer skin models. This is achievable due to the instant polymerization of the keratinocytes and fibroblast combination that allows a direct application on the wound. We suggest that the polymerizable skin hydrogel is an inexpensive, easy and rapid treatment that could be transferred into clinical practice in order to improve the treatment of skin wounds. Full article

(This article belongs to the Special Issue Dermal Research: From Molecular Mechanisms to Pathology)

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Review

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12 pages, 557 KiB

Open AccessReview

Bacterial Motility and Its Role in Skin and Wound Infections

by Katarzyna Zegadło, Monika Gieroń, Paulina Żarnowiec, Katarzyna Durlik-Popińska, Beata Kręcisz, Wiesław Kaca and Grzegorz Czerwonka

Int. J. Mol. Sci. 2023, 24(2), 1707; https://doi.org/10.3390/ijms24021707 - 15 Jan 2023

Cited by 14 | Viewed by 7934

Abstract

Skin and wound infections are serious medical problems, and the diversity of bacteria makes such infections difficult to treat. Bacteria possess many virulence factors, among which motility plays a key role in skin infections. This feature allows for movement over the skin surface [...] Read more.

Skin and wound infections are serious medical problems, and the diversity of bacteria makes such infections difficult to treat. Bacteria possess many virulence factors, among which motility plays a key role in skin infections. This feature allows for movement over the skin surface and relocation into the wound. The aim of this paper is to review the type of bacterial movement and to indicate the underlying mechanisms than can serve as a target for developing or modifying antibacterial therapies applied in wound infection treatment. Five types of bacterial movement are distinguished: appendage-dependent (swimming, swarming, and twitching) and appendage-independent (gliding and sliding). All of them allow bacteria to relocate and aid bacteria during infection. Swimming motility allows bacteria to spread from ‘persister cells’ in biofilm microcolonies and colonise other tissues. Twitching motility enables bacteria to press through the tissues during infection, whereas sliding motility allows cocci (defined as non-motile) to migrate over surfaces. Bacteria during swarming display greater resistance to antimicrobials. Molecular motors generating the focal adhesion complexes in the bacterial cell leaflet generate a ‘wave’, which pushes bacterial cells lacking appendages, thereby enabling movement. Here, we present the five main types of bacterial motility, their molecular mechanisms, and examples of bacteria that utilise them. Bacterial migration mechanisms can be considered not only as a virulence factor but also as a target for antibacterial therapy. Full article

(This article belongs to the Special Issue Dermal Research: From Molecular Mechanisms to Pathology)

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21 pages, 1047 KiB

Open AccessReview

Zinc and Zinc Transporters in Dermatology

by Zubaidah Al-Khafaji, Sofia Brito and Bum-Ho Bin

Int. J. Mol. Sci. 2022, 23(24), 16165; https://doi.org/10.3390/ijms232416165 - 18 Dec 2022

Cited by 5 | Viewed by 3897

Abstract

Zinc is an important trace mineral in the human body and a daily intake of zinc is required to maintain a healthy status. Over the past decades, zinc has been used in formulating topical and systemic therapies for various skin disorders owing to [...] Read more.

Zinc is an important trace mineral in the human body and a daily intake of zinc is required to maintain a healthy status. Over the past decades, zinc has been used in formulating topical and systemic therapies for various skin disorders owing to its wound healing and antimicrobial properties. Zinc transporters play a major role in maintaining the integrity of the integumentary system by controlling zinc homeostasis within dermal layers. Mutations and abnormal function of zinc-transporting proteins can lead to disease development, such as spondylocheirodysplastic Ehlers–Danlos syndrome (SCD-EDS) and acrodermatitis enteropathica (AE) which can be fatal if left untreated. This review discusses the layers of the skin, the importance of zinc and zinc transporters in each layer, and the various skin disorders caused by zinc deficiency, in addition to zinc-containing compounds used for treating different skin disorders and skin protection. Full article

(This article belongs to the Special Issue Dermal Research: From Molecular Mechanisms to Pathology)

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23 pages, 1551 KiB

Open AccessReview

The Microbiome in Systemic Sclerosis: Pathophysiology and Therapeutic Potential

by Suhee Kim, Hee Jin Park and Sang-Il Lee

Int. J. Mol. Sci. 2022, 23(24), 16154; https://doi.org/10.3390/ijms232416154 - 18 Dec 2022

Cited by 3 | Viewed by 2985

Abstract

Systemic sclerosis (SSc), also known as scleroderma, is an autoimmune disease with unknown etiology characterized by multi-organ fibrosis. Despite substantial investigation on SSc-related cellular and molecular mechanisms, effective therapies are still lacking. The skin, lungs, and gut are the most affected organs in [...] Read more.

Systemic sclerosis (SSc), also known as scleroderma, is an autoimmune disease with unknown etiology characterized by multi-organ fibrosis. Despite substantial investigation on SSc-related cellular and molecular mechanisms, effective therapies are still lacking. The skin, lungs, and gut are the most affected organs in SSc, which act as physical barriers and constantly communicate with colonized microbiota. Recent reports have documented a unique microbiome signature, which may be the pathogenic trigger or driver of SSc. Since gut microbiota influences the efficacy and toxicity of oral drugs, evaluating drug–microbiota interactions has become an area of interest in disease treatment. The existing evidence highlights the potential of the microbial challenge as a novel therapeutic option in SSc. In this review, we have summarized the current knowledge about molecular mechanisms of SSc and highlighted the underlying role of the microbiome in SSc pathogenesis. We have also discussed the latest therapeutic interventions using microbiomes in SSc, including drug–microbiota interactions and animal disease models. This review aims to elucidate the pathophysiological connection and therapeutic potential of the microbiome in SSc. Insights into the microbiome will significantly improve our understanding of etiopathogenesis and developing therapeutics for SSc. Full article

(This article belongs to the Special Issue Dermal Research: From Molecular Mechanisms to Pathology)

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16 pages, 1494 KiB

Open AccessReview

Role of Inflammasomes in Keloids and Hypertrophic Scars—Lessons Learned from Chronic Diabetic Wounds and Skin Fibrosis

by Chenyu Huang and Rei Ogawa

Int. J. Mol. Sci. 2022, 23(12), 6820; https://doi.org/10.3390/ijms23126820 - 19 Jun 2022

Cited by 19 | Viewed by 3632

Abstract

Keloids and hypertrophic scars are pathological cutaneous scars. They arise from excessive wound healing, which induces chronic dermal inflammation and results in overwhelming fibroblast production of extracellular matrix. Their etiology is unclear. Inflammasomes are multiprotein complexes that are important in proinflammatory innate-immune system [...] Read more.

Keloids and hypertrophic scars are pathological cutaneous scars. They arise from excessive wound healing, which induces chronic dermal inflammation and results in overwhelming fibroblast production of extracellular matrix. Their etiology is unclear. Inflammasomes are multiprotein complexes that are important in proinflammatory innate-immune system responses. We asked whether inflammasomes participate in pathological scarring by examining the literature on scarring, diabetic wounds (also characterized by chronic inflammation), and systemic sclerosis (also marked by fibrosis). Pathological scars are predominantly populated by anti-inflammatory M2 macrophages and recent literature hints that this could be driven by non-canonical inflammasome signaling. Diabetic-wound healing associates with inflammasome activation in immune (macrophages) and non-immune (keratinocytes) cells. Fibrotic conditions associate with inflammasome activation and inflammasome-induced transition of epithelial cells/endothelial cells/macrophages into myofibroblasts that deposit excessive extracellular matrix. Studies suggest that mechanical stimuli activate inflammasomes via the cytoskeleton and that mechanotransduction-inflammasome crosstalk is involved in fibrosis. Further research should examine (i) the roles that various inflammasome types in macrophages, (myo)fibroblasts, and other cell types play in keloid development and (ii) how mechanical stimuli interact with inflammasomes and thereby drive scar growth. Such research is likely to significantly advance our understanding of pathological scarring and aid the development of new therapeutic strategies. Full article

(This article belongs to the Special Issue Dermal Research: From Molecular Mechanisms to Pathology)

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Other

Jump to: Research, Review

7 pages, 2151 KiB

Open AccessCase Report

Mast Cells Are Activated in the Giant Earlobe Keloids: A Case Series

by Yukari Nakajima, Noriko Aramaki, Nao Takeuchi, Ayumi Yamanishi, Yoshiko Kumagai, Keisuke Okabe, Tomoaki Yokoyama and Kazuo Kishi

Int. J. Mol. Sci. 2022, 23(18), 10410; https://doi.org/10.3390/ijms231810410 - 8 Sep 2022

Viewed by 1470

Abstract

Mast cells and inflammatory cells are abundant in keloid and hypertrophic scar tissues. Even if the cause of physical injury is similar, such as piercing or scratching with hands, clinical findings show differences in the size of keloids in the same area. Hence, [...] Read more.

Mast cells and inflammatory cells are abundant in keloid and hypertrophic scar tissues. Even if the cause of physical injury is similar, such as piercing or scratching with hands, clinical findings show differences in the size of keloids in the same area. Hence, we performed histological studies on giant keloids larger than the earlobe, and other smaller keloids. We also examined the risk factors associated with the formation of giant lesions. No statistically significant differences in the association of the risk factors were observed. However, histological observations clearly showed a high number of degranulated or active mast cells with a trend towards a greater number of degranulated mast cells in the giant keloid tissues. Collagen production also tended to increase. Two patients with giant keloids were severely obese, suggesting that the persistent inflammatory state of obesity may also be involved in the growth of keloid lesions. Full article

(This article belongs to the Special Issue Dermal Research: From Molecular Mechanisms to Pathology)

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