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Nature Metabolism Jan 2019Extracellular matrix (ECM) homeostasis is essential for normal tissue function, and its disruption by iatrogenic injury, trauma, or disease results in fibrosis. Skin ECM...
Extracellular matrix (ECM) homeostasis is essential for normal tissue function, and its disruption by iatrogenic injury, trauma, or disease results in fibrosis. Skin ECM homeostasis is maintained by a complex process that involves an integration of cytokine and environmental mediators. However, it is unclear, in both normal and disease states, how these multifactorial processes converge to shift ECM homeostasis towards accumulation or degradation. Here we show a consistent downregulation in fatty acid oxidation (FAO) and upregulation of glycolysis in fibrotic skin and in normal skin with abundant ECM. Perturbation of glycolysis and FAO pathway enzymes reveals their reciprocal effects in ECM upregulation and downregulation, respectively. Increasing peroxisome proliferator-activated receptor (PPAR) signalling, an inducer of the FAO pathway, generates a catabolic fibroblast phenotype characterised by inhibition of ECM transcription and enhanced ECM internalization and lysosomal degradation. In contrast, suppression of glycolysis inhibits ECM gene transcription and protein levels, independently of an intact FAO pathway or PPAR signalling. Moreover, we show that CD36, a multifunctional fatty acid transporter, connects the metabolic state of fibroblasts with their capacity for ECM regulation, as internalization and degradation of collagen-1 is abrogated in fibroblasts lacking CD36. Finally, restoring FAO and upregulating CD36 reduces ECM accumulation in murine skin fibrosis. These findings indicate that metabolic perturbation of ECM homeostasis may have broad implications for therapies aimed at ECM regulation, such as fibrosis, regenerative medicine, and ageing.
Topics: Biomarkers; Cells, Cultured; Computational Biology; Dermis; Energy Metabolism; Extracellular Matrix; Fibroblasts; Gene Expression Profiling; Glycolysis; Homeostasis; Models, Biological
PubMed: 32694814
DOI: 10.1038/s42255-018-0008-5 -
Journal of Biomedical Optics Sep 2018The use of multiphoton imaging has become a standard technique to visualize the dermis fibers as it requires no specific staining. The density and organization of...
The use of multiphoton imaging has become a standard technique to visualize the dermis fibers as it requires no specific staining. The density and organization of collagen and elastin are common markers of skin intrinsic aging and photoaging; thus, there is a need of grading this skin aging with quantitative indicators able to provide a robust evaluation of the dermis fibers' state. We propose a systematic analysis of multiphoton images of skin biopsies taken on the buttock and the forearm of patients of different ages. The intensity histograms of images were analyzed through their moments, a wavelet decomposition was done, and the wavelet coefficients distribution was fitted by a generalized Gaussian distribution. Different parameters relative to the collagen or elastin densities, organizations, and structures were calculated and exhibit phenomena specific to intrinsic or extrinsic aging. Those indicators could become a standard method to analyze the degree of skin aging (intrinsic or extrinsic) through multiphoton imaging.
Topics: Adult; Collagen; Dermis; Elastin; Humans; Image Processing, Computer-Assisted; Microscopy, Fluorescence, Multiphoton; Middle Aged; Signal Processing, Computer-Assisted; Skin Aging; Young Adult
PubMed: 30244547
DOI: 10.1117/1.JBO.23.9.096501 -
International Journal of Molecular... Dec 2017Zinc (Zn), which is an essential trace element, is involved in numerous mammalian physiological events; therefore, either a deficiency or excess of Zn impairs cellular... (Review)
Review
Zinc (Zn), which is an essential trace element, is involved in numerous mammalian physiological events; therefore, either a deficiency or excess of Zn impairs cellular machineries and influences physiological events, such as systemic growth, bone homeostasis, skin formation, immune responses, endocrine function, and neuronal function. Zn transporters are thought to mainly contribute to Zn homeostasis within cells and in the whole body. Recent genetic, cellular, and molecular studies of Zn transporters highlight the dynamic role of Zn as a signaling mediator linking several cellular events and signaling pathways. Dysfunction in Zn transporters causes various diseases. This review aims to provide an update of Zn transporters and Zn signaling studies and discusses the remaining questions and future directions by focusing on recent progress in determining the roles of SLC39A/ZIP family members in vivo.
Topics: Animals; B-Lymphocytes; Carrier Proteins; Cation Transport Proteins; Dermis; Humans; Intestinal Mucosa; Signal Transduction; Zinc
PubMed: 29236063
DOI: 10.3390/ijms18122708 -
The Journal of Pathology Mar 2021The dermis has disparate embryonic origins; abdominal dermis develops from lateral plate mesoderm, dorsal dermis from paraxial mesoderm and facial dermis from neural...
The dermis has disparate embryonic origins; abdominal dermis develops from lateral plate mesoderm, dorsal dermis from paraxial mesoderm and facial dermis from neural crest. However, the cell and molecular differences and their functional implications have not been described. We hypothesise that the embryonic origin of the dermis underpins regional characteristics of skin, including its response to wounding. We have compared abdomen, back and cheek, three anatomical sites representing the distinct embryonic tissues from which the dermis can arise, during homeostasis and wound repair using RNA sequencing, histology and fibroblast cultures. Our transcriptional analyses demonstrate differences between body sites that reflect their diverse origins. Moreover, we report histological and transcriptional variations during a wound response, including site differences in ECM composition, cell migration and proliferation, and re-enactment of distinct developmental programmes. These findings reveal profound regional variation in the mechanisms of tissue repair. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.
Topics: Animals; Dermis; Homeostasis; Mice; Wound Healing
PubMed: 33197044
DOI: 10.1002/path.5589 -
Indian Journal of Dermatology,... 2018
Review
Topics: Dermis; Diagnosis, Differential; Epidermis; Foreign-Body Reaction; Humans; Skin Diseases; Transendothelial and Transepithelial Migration
PubMed: 30073986
DOI: 10.4103/ijdvl.IJDVL_396_17 -
The American Journal of Dermatopathology Mar 2022Primary dermal melanoma (PDM) is defined as a primary melanoma tumor confined to the dermis, subcutis, or both, without epidermal involvement. The significant overlap of...
Primary dermal melanoma (PDM) is defined as a primary melanoma tumor confined to the dermis, subcutis, or both, without epidermal involvement. The significant overlap of histopathological features in PDM and cutaneous metastatic melanoma makes diagnostic accuracy of PDM challenging. We present a case of a 48-year-old man with a nontender 1.5 × 1.5 cm subcutaneous nodule on the left leg, which had been present for years. Biopsy revealed a dermal tumor with melanocytic differentiation noted to be positive for SOX-10. Additional pathology findings included a high Ki-67 proliferation index and a loss of p16 expression. Pathology reports were consistent with primary tumor stage 4a, and the patient was referred to surgical oncology where examination and workup demonstrated no evidence of the residual lesion representing a metastasis from a primary site. As PDM is histologically indistinguishable from melanoma metastasis to the skin, clues including a history of an evolving subepidermal nodule and exclusion of previous or concurrent melanomas can assist in its accurate diagnosis. Currently, a consensus on the criteria, staging, and management of PDM does not exist. Poorly defined diagnostic criteria and general lack of awareness of PDM result in high rates of incorrect and late-stage diagnoses. This case report highlights the importance of physician familiarity with PDM to ensure accurate recognition, evidence-based management, and improved patient outcomes.
Topics: Dermis; Humans; Male; Melanoma; Middle Aged; Subcutaneous Tissue
PubMed: 34726186
DOI: 10.1097/DAD.0000000000002099 -
Marine Drugs Feb 2023The catch connective, or mutable collagenous, tissue of echinoderms changes its mechanical properties in response to stimulation. The body wall dermis of sea cucumbers... (Review)
Review
The catch connective, or mutable collagenous, tissue of echinoderms changes its mechanical properties in response to stimulation. The body wall dermis of sea cucumbers is a typical catch connective tissue. The dermis assumes three mechanical states: soft, standard, and stiff. Proteins that change the mechanical properties have been purified from the dermis. Tensilin and the novel stiffening factor are involved in the soft to standard and standard to stiff transitions, respectively. Softenin softens the dermis in the standard state. Tensilin and softenin work directly on the extracellular matrix (ECM). This review summarizes the current knowledge regarding such stiffeners and softeners. Attention is also given to the genes of tensilin and its related proteins in echinoderms. In addition, we provide information on the morphological changes of the ECM associated with the stiffness change of the dermis. Ultrastructural study suggests that tensilin induces an increase in the cohesive forces with the lateral fusion of collagen subfibrils in the soft to standard transition, that crossbridge formation between fibrils occurs in both the soft to standard and standard to stiff transitions, and that the bond which accompanies water exudation produces the stiff dermis from the standard state.
Topics: Animals; Dermis; Echinodermata; Connective Tissue; Collagen; Extracellular Matrix
PubMed: 36976189
DOI: 10.3390/md21030140 -
The Journal of Investigative Dermatology May 2019Dermal white adipose tissue is a unique layer of adipocytes within the reticular dermis of the skin. Recently, several nonmetabolic activities have been discovered for... (Review)
Review
Dermal white adipose tissue is a unique layer of adipocytes within the reticular dermis of the skin. Recently, several nonmetabolic activities have been discovered for dWAT and its fibroblast precursors. These functions include antimicrobial defense and roles in hair cycling, wound healing, and thermogenesis. In this review, we discuss recent progress in understanding the role of dermal white adipose tissue in immunity, both as an innate antimicrobial cell type and as an indirect communicator with other cutaneous immunocytes to enhance defense and potentially contribute to inflammatory disease.
Topics: Adipose Tissue, White; Animals; Dermis; Female; Humans; Immunity, Innate; Male; Sensitivity and Specificity; Skin; Wound Healing; Wounds and Injuries
PubMed: 30879642
DOI: 10.1016/j.jid.2018.12.031 -
The American Journal of Dermatopathology Jul 2015Elastoderma is a rare cutaneous condition, which clinically presents as an acquired laxity and decreased recoil of skin. It is histologically characterized by an... (Review)
Review
Elastoderma is a rare cutaneous condition, which clinically presents as an acquired laxity and decreased recoil of skin. It is histologically characterized by an increase of pleomorphic and fragmented elastic fibers in the superficial dermis. A case of a 61-year-old woman with wrinkled lax skin on the anterior and lateral aspects of her neck was reported. Microscopic examination revealed an accumulation of fragmented curled elastic fibers in the dermis. This is the fifth reported case of elastoderma.
Topics: Anetoderma; Dermis; Elastic Tissue; Female; Humans; Middle Aged; Neck
PubMed: 25072684
DOI: 10.1097/DAD.0000000000000146 -
The Journal of the American Osteopathic... Mar 2015
Topics: Aged; Biopsy; Dermis; Herpes Zoster; Herpesvirus 3, Human; Humans; Male
PubMed: 25722364
DOI: 10.7556/jaoa.2015.034