Journal Of Investigative Dermatology

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934 The mechanism of platelet-rich plasma in uvr-induced dermal tissue injury and repair: Adjusting the macrophage polarization through activin receptor-follistatin system

Wed, 2019-05-01 00:00
As a common extrinsic factor, ultraviolet radiation(UVR) can induce dermal tissue injury, in which case macrophages can be polarized into M1 and M2 for different stages. Activin A has been proved stimulating the polarization of M2 with the co-regulation of FST and ACVR II. Clinically, PRP shows significant efficacy in wound repair with the induction of Activin A. Therefore, we intend to study the mechanism about PRP in UVR-induced dermal tissue injury and repair, whether PRP can adjust macrophage polarization through ACVRII-FST system, and provide further theoretical evidence for its application in dermatology.

933 TRAF4 promotes fibroblast proliferation in keloids by destabilizing p53 via interacting with the deubiquitinase USP10

Wed, 2019-05-01 00:00
Keloids represent an extreme of aberrant dermal wound healing, characterized by excessive fibroblast proliferation. However, the mechanism of fibroproliferation remains elusive. Here, we showed that TRAF4 was highly expressed in keloid fibroblasts and promoted fibroproliferation. Independent of its E3 ubiquitin ligase activity, TRAF4 suppressed p53 pathway instead of mediating TGFβ pathway. In details, TRAF4 interacted with the deubiquitinase USP10 and blocked the access of p53 to USP10, resulting in p53 destabilization.

932 Development of an early wound model in human ex vivo skin explant as a preclinical model of wound healing

Wed, 2019-05-01 00:00
This study characterizes the potential of an ex vivo model with human skin explant to mimic cutaneous wounds and healing for the testing of potential topical therapeutics. Freshly excised healthy human skin from abdominoplasty was wounded via punch biopsy and cultured to determine the time course for wound-associated biomarkers by RT-qPCR and visual re-epithelization by hematoxylin and eosin staining. A distinct time dependent profile evaluating 9 well-established biomarkers in cutaneous wounding and healing was observed both in the center and the peripheral area of the wound.

931 Distinct regulatory transcriptional profiles reveal a wound healing phenotype for inflammatory macrophages exposed to TNF-Adalimumab complexes in vitro

Wed, 2019-05-01 00:00
Adalimumab (ADA) is the only FDA-approved treatment for moderate to severe hidradenitis suppurativa (HS), a chronic inflammatory disease characterized by recurrent abscesses/nodules and draining wounds. However, the pathogenic role of TNFα and the mechanism of action (MOA) of adalimumab in HS wound healing remain unknown. We have previously demonstrated that TNF-adalimumab complexes show stronger inhibitory effect on inflammatory macrophage (M1 Mφ) development by diverting these cells towards a wound healing (M2) Mφ phenotype in comparison with TNF-etanercept (ETN) or TNF-certolizumab pegol (CZP) complexes.

930 SOX2 epidermal overexpression promotes cutaneous wound healing via activation of EGFR/MEK/ERK signaling mediated by EGFR ligands

Wed, 2019-05-01 00:00
Oral mucosa contains a unique transcriptional network that primes oral wounds for rapid resolution in humans. Our previous work identified genes that were consistently upregulated in the oral mucosa and demonstrated that induction of one of the identified genes, transcription factor SOX2, promoted cutaneous wound healing in mice. In this study, we investigated the molecular and cellular mechanisms by which SOX2 accelerates wound healing in skin. RNA-seq analysis showed that SOX2 induced a proliferative and wound-activated phenotype in skin keratinocytes prior to wounding.

929 The role of XEDAR in the development and evolution of mammary gland phenotypes

Wed, 2019-05-01 00:00
Human skin is populated by a variety of ectodermal appendages, including hair follicles, eccrine glands and mammary glands. The Ectodysplasin (EDA) pathway is one of the major regulators of ectodermal appendage formation. Accordingly, mutations in the EDA pathway are causal to the development of ectodermal dysplasia in humans and underlie evolutionary variation in ectodermal appendage phenotypes between populations. These effects have been largely attributed to a splice variant of the EDA gene which encodes the ligand EDA-A1 and also to its receptor EDAR.

928 Characterisation of the mouse embryonic dermis and timing and control of adipogenic cell fate

Wed, 2019-05-01 00:00
Embryonic mouse dermis changes from an apparently homogenous early cell population to heterogenous progeny that contribute to papillary, reticular and follicular dermal compartments, by late embryogenesis. However, precise timing of these events is unclear, and up to now literature on dermal white adipose tissue (DWAT), which develops in the lower dermis, has focused on events as late as embryonic day 16.5 (E16.5) when cells expressing the adipogenic transcription factor C/ebp-α restrict to the lower dermis.

927 The path from skin to fat: Is adipocyte differentiation the default lineage for embryonic dermal cells?

Wed, 2019-05-01 00:00
Embryonic dermal identity and the intrinsic and extrinsic factors that control dermal cell fate remain relatively unknown, as does developmental timing of these events. Ultimately, however, cells of the upper dermis become fibroblasts/hair follicle dermis, while dermal white adipose tissue (DWAT) originates from the lower dermis. To investigate the molecular cues that influence dermal development we established a 3D spheroid culture model from enzymatically isolated E13.5 mouse dermis. Interestingly, the adipogenic potential of 2D and 3D dermal cells differed in-vitro.

926 Keratin 17: A novel regulator of nuclear morphology and chromatin organization

Wed, 2019-05-01 00:00
We and others discovered the presence of a type I intermediate filament protein, keratin 17 (K17), in the nucleus of tumor epithelial cells, where it participates in transcriptional regulation and cell cycle progression. Here we report on K17-dependent differences in morphological attributes of the nucleus, leading us to hypothesize that K17 regulates nuclear architecture and chromatin organization. Relative to controls, KRT17 null epithelial cells exhibit more flattened nuclei with a corresponding increase in nuclear surface area but no change in overall volume.

925 Small molecule targeting of multiple signaling pathways for hair follicle formation from mouse neonatal cells

Wed, 2019-05-01 00:00
Alopecia, or hair loss, is a condition of diverse origins, from genetic underpinnings to scarring arising from inflammation or trauma. Current treatments modulate hair growth by influencing existing precursor populations, however treatments aimed at de-novo production of hair follicles remain elusive. An in-vitro model studying de-novo human hair follicle formation from iPS cells or adult cells would open the potential for such novel treatments to be identified and tested. Due to the similarities between human and mouse hair follicles during development, we aimed to optimize current in-vitro conditions for de-novo murine hair follicle formation from neonatal cells.

924 Efficient genome editing using CRISPR/Cas9 ribonucleoprotein approach in iPS cells for recessive dystrophic epidermolysis bullosa

Wed, 2019-05-01 00:00
Recessive dystrophic epidermolysis bullosa (RDEB) is a severe inherited skin disorder caused by mutations in the COL7A1 gene encoding type VII collagen (C7), the major constituent of anchoring fibrils (AFs) at the basement membrane zone (BMZ). Patients with RDEB lack functional C7 and have severely impaired dermal-epidermal stability. This results in extensive blistering and open wounds on the skin which greatly affect the patients’ quality of life. There are currently no therapies approved for the treatment of RDEB.

923 Molecular phenotyping of lichen planopilaris revealed dysregulation of cholesterol/fatty acid metabolism, fibrosis and mast cell pathways

Wed, 2019-05-01 00:00
Lichen planopilaris (LPP) is a primary lymphocytic scarring alopecia whose incidence and prevalence are poorly defined. The literature reports LPP patients comprise <1%-8% of annual new referrals to tertiary hair centers, with a reported 2:1 to 4:1 female predominance. Clinically, LPP is characterized by burning, inflammation and scarring hair loss in a patchy distribution over the scalp. Expert opinion currently guides accepted therapies, therefore most patients opting for treatment are given individually or a combination of topical or injection corticosteroids, antibiotics, and hydroxychloroquine.

922 Dermal white adipose tissue secretes hepatocyte growth factor to promote human hair follicle growth and pigmentation

Wed, 2019-05-01 00:00
Although human dermal white adipose tissue (DWAT) envelopes scalp hair follicles (HFs), their underlying bidirectional communication remains unexplored. Recently, we determined that culturing human HFs with surrounding DWAT promoted hair growth and pigmentation ex vivo. The current study aimed to further expand knowledge of the human DWAT-HF axis. Intriguingly, proteomic analysis identified hepatocyte growth factor (HGF) as the most abundantly-secreted DWAT product within long-term HF+DWAT ex vivo cultures.

921 Generation of a new rodent model of scleroderma

Wed, 2019-05-01 00:00
Scleroderma is characterized by unresolving fibrosis of the dermis and loss of hair follicles. We report the generation of a new mouse model that exhibits features of scleroderma including skin thickening, dermal fibrosis, loss of dermal white adipose tissue and alopecia. A ‘silent’ transgene with no functional transcript was randomly integrated into the mouse genome. Mice that are hemizygous for the transgene insertion developed normally; however, littermates that are homozygous for the transgene remained hairless.

920 The non-coding control region of Trichodysplasia spinulosa polyomavirus is responsible for cell-type specific viral gene expression in vivo

Wed, 2019-05-01 00:00
Trichodysplasia spinulosa is a rare hair follicle disorder that develops in immunosuppressed patients and is associated with productive infection by a polyomavirus designated TSPyV. Affected hair follicles contain a crescent-like hair matrix, a massively expanded compartment of aberrantly proliferating inner root sheath (IRS)-like cells, and disorganized hair shaft-like cells. The TSPyV genome contains an early region encoding transforming antigens (TAgs) responsible for viral genome replication, and the late region encoding structural proteins needed for assembly of virions during productive infection.

919 Overexpression of cyclooxygenase-2 in the skin of adult transgenic mice leads to sebaceous gland hyperplasia and thinning of hair shafts

Wed, 2019-05-01 00:00
Current methods of modeling androgenetic alopecia (AGA), or male pattern baldness as it is more commonly known, in mice have used the constitutive expression of cyclooxygenase-2 (COX-2), an enzyme involved in the synthesis of prostaglandin D2 (PGD2), which is known to inhibit hair growth. However, this model cannot determine the effect of induced COX-2 expression in adult mice, which is of particular importance given that pathogenesis of AGA presents in mature hair follicles, nor can it determine whether a normal hair phenotype can subsequently be recovered after reducing COX-2 expression.

918 Skin morphogenesis by coupling biochemical-bioelectric signals: Calcium oscillations coordinate dermal cell movement by epidermis-derived SHH signaling during feather bud orientation

Wed, 2019-05-01 00:00
Tissue morphogenesis during development and wound healing may involve bio-electric mechanisms, but much is unknown. Using the developing chicken skin model, we found feather bud orientations, as a single bud and collectively as a population, are accompanied by dynamic changes of endogenous bioelectric current landscapes. Transcriptome profiling and functional assays implicate contributions from functional voltage-gated Ca2+ channels (VGCCs), Connexin-43 based gap junctions, and Ca2+ release activated Ca2+ (CRAC) channels.

917 Frontal fibrosing alopecia scalp profiling links Th1/Th2 and JAK3 activation with fibrosis and loss of follicular stem cells

Wed, 2019-05-01 00:00
Frontal Fibrosing Alopecia/FFA is a subtype of alopecia with unknown pathogenesis, lacking efficacious therapeutics. Current models emphasize fibrosis as the primary disease mechanism. We profiled FFA scalp biopsies as compared to alopecia areata/AA and control scalp biopsies, using protein and gene-expression studies. Lesional and non-lesional scalp biopsies were taken from FFA (n=12), AA (n=10) patients and normal scalp (n=3) from controls. We found significant increases in CD8+ T cytotoxic cells and CD11c+ dendritic cell infiltrates in FFA and AA versus control scalp (p<0.05), with corresponding elevations in granzyme B mRNA, particularly in FFA tissues (p<0.01).

916 Gynecologic and hormonal comorbidities of scarring alopecia: A retrospective review

Wed, 2019-05-01 00:00
Scarring alopecias, including frontal fibrosing alopecia (FFA), lichen planopilaris (LPP), and central centrifugal cicatricial alopecia (CCCA), involve destruction of the hair follicle unit which results in permanent hair loss. It is suspected that environmental, genetic, and hormonal influences contribute to the development of these diseases. This retrospective review thus sought to identify differences in gynecologic and hormonal comorbidities in patients with scarring alopecia in comparison to those with female pattern hair loss (FPHL), a form of non-scarring alopecia.

915 Dietary grape powder inhibits atopic dermatitis-like skin lesions in NC/Nga mice

Wed, 2019-05-01 00:00
Atopic dermatitis (AD) is a common and chronic pruritic skin disorder that significantly diminishes the quality of life of affected patients. In a 13-week study, we determined potential efficacy of dietary grape powder (GP; 3 or 5%) on 2,4-dinitrofluorobenzene (DNFB)-induced skin lesions in the NC/NgaTndCrlj mouse model of AD in prevention (start GP diet on day 1) and intervention (start GP diet at AD onset, 6 weeks) settings. Gross assessment of lesion progression demonstrated that GP markedly inhibited development and progression of visually evident skin lesions in both settings.

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