Skin Appendages Research Articles

Significance of Dermoscopy in Association with Clinical Features in Differentiation of Basal Cell Carcinoma and Benign Trichoblastic Tumours.

Simple SummaryAlthough basal cell carcinoma (BCC) can, in the majority of cases, be diagnosed based on clinical and dermoscopic assessment, a potential overlap with benign adnexal skin tumours seems to exist, including trichoblastic tumours (TT). The aim of this study was to analyse clinical and dermoscopic features of benign TT and BCC to develop a diagnostic algorithm with a potential utility in clinical practice. Despite differences in frequency of clinical and dermoscopic features between BCC and TT in the studied group, differential diagnosis based on these variables is not reliable. Histopathological examination remains a diagnostic gold standard in differentiation of BCC and TT.Background: Although basal cell carcinoma (BCC) can, in the majority of cases, be diagnosed based on clinical and dermoscopic assessment, a potential overlap with benign adnexal skin tumours seems to exist, including trichoblastic tumours (TT). Methods: Retrospective analysis of clinical and dermoscopic features of benign TT and BCC cases was performed to develop a diagnostic algorithm with a potential utility in clinical practice. Results: In the study, 502 histopathologically confirmed BCC cases were compared with 61 TT (including 44 TB (72.13%), 10 TE (16.39%) and 7 DTE (11.48%]). Patients in the BCC group were statistically older (mean age was 71.4 vs. 64.4 years, respectively; p = 0.009). BCC presented generally as larger tumours (mean tumour size 11.0 vs. 8.2 mm for the TT group; p = 0.001) and was more frequently associated with clinically visible ulceration (59.4% vs. 19.7%, respectively; p < 0.001). Comparison of lesion morphology, clinically visible pigmentation, and anatomical location did not show significant differences between the analysed groups. Dermoscopically visible ulceration was significantly more common in the BCC group compared to the TT group (52.2% vs. 14.8%; p < 0.0001). Pigmented structures, specifically brown dots and brown globules, were significantly more prevalent in the TT group (32.8% vs. 11.4%; p = 0.0001 and 29.5% vs. 8.2%; p <0.0001). Similarly, TT more commonly than BCC showed the presence of cloudy/starry milia-like cysts (26.2% vs. 11.6%; p = 0.0031) and yellow globules (16.4% vs. 7.2%; p = 0.033). Conclusions: Despite differences in frequency of clinical and dermoscopic features between BCC and TT in the studied group, differential diagnosis based on these variables is not reliable. Histopathological examination remains a diagnostic gold standard in differentiation of BCC and TT.

Differential distribution and genetic determination of eccrine sweat glands and hair follicles in the volar skin of C57BL/6 mice and SD rats

BackgroundEccrine sweat glands (ESGs) and hair follicles (HFs) are the prominent skin appendages regulating human body temperature. C57BL/6 mice and Sprague–Dawley (SD) rats are the most commonly used model animals for studying ESGs and HFs. Previous studies have shown the distribution of ESGs and HFs in volar hindfeet of C57BL/6 mice, but there are few or no reports on the distribution of ESGs and HFs in volar forefeet of C57BL/6 mice and volar feet of SD rats. Here, we investigated the differential distribution and genetic determination of ESGs and HFs in the volar skin of C57BL/6 mice and SD rats through gross observation, iodine-starch sweat test, double staining with Nile Blue A and Oil Red O, hematoxylin and eosin (HE) staining, double immunofluorescence staining of LIM Homeobox 2 (LHX2)/Na+-K+-ATPase α1(NKA) or LHX2/Na+-K+-2Cl－ cotransporter 1 (NKCC1), and qRT-PCR detection of ESG-related gene Engrailed 1 (En1) and HF-related gene LHX2.ResultsThe results showed ESGs but no HFs in the footpads of C57BL/6 mice and SD rats, both ESGs and HFs in the inter-footpads (IFPs) of C57BL/6 mice, and neither ESGs nor HFs in the IFPs of SD rats. The relative quantitative change in En1 was consistent with the differential distribution of ESGs, and the relative quantitative change of LHX2 was consistent with the differential distribution of HFs.ConclusionC57BL/6 mice and SD rats had their own characteristics in the distribution of ESGs and HFs in the volar skin, and researchers should choose mice or rats, and even forefeet or hindfeet as their research object according to different purposes. The study provides a basis for selection of optimal animal models to study development, wound healing and regeneration of skin appendages.

Silk Fibroin-Based Bioengineered Scaffold for Enabling Hemostasis and Skin Regeneration of Critical-Size Full-Thickness Heat-Induced Burn Wounds.

Millions of people around the globe are affected by full-thickness skin injuries. A delay in the healing of such injuries can lead to the formation of chronic wounds, posing several clinical and economic challenges. Current strategies for wound care aim for skin regeneration and not merely skin repair or faster wound closure. The present study aimed to develop a bioactive wound-healing matrix comprising natural biomaterial silk fibroin (SF), clinical-grade human fibrin (FIB), and human hyaluronic acid (HA), resulting in SFFIBHA for regeneration of full-thickness burn wounds. A porous, hemostatic, self-adhesive, moisture-retentive, and biomimetic scaffold that promotes healing was the expected outcome. The study validated a terminal sterilization method, suggesting the stability and translational potential of the novel scaffold. Also, the study demonstrated the regenerative abilities of scaffolds using in vitro cell culture experiments and in vivo full-thickness burn wounds of critical size (4 cm × 4 cm) in a rabbit model. Under in vitro conditions, the scaffold enhanced primary dermal fibroblast adhesion and cell proliferation with regulated extracellular matrix (ECM) synthesis. In vivo, the scaffolds promoted healing with mature epithelium coverage involving intact basal cells, superficial keratinocytes, multilayers of keratohyalin, dermal regeneration with angiogenesis, and deposition of remodeled ECM in 28 days. The relative gene expression of the IL6 marker indicated transitions from inflammation to proliferation stage. In addition, we observed skin appendages and rete peg development in the SFFIBHA-treated wound tissues. Although wound closure was observed, neither negative (untreated/sham) nor positive (commercially available product; NeuSkin) control wounds developed skin appendages/rete pegs or native skin architecture. After 56 days, healing with organized ECM production enabled the recovery of mechanical properties of skin with higher tissue maturity in SFFIBHA-treated wounds. Thus, in a single application, the SFFIBHA scaffold proved to be an efficient biomimetic matrix that can guide burn wound regeneration. The developed matrix is a suture-less, hemostatic, off-the-shelf product for potential wound regenerative applications.

Angiosarcoma-like Kaposi Sarcoma: A Distinctive Histomorphologic Variant Representing an Important Diagnostic Pitfall.

Kaposi sarcoma (KS) is a rare low-grade angioproliferative neoplasm associated with human herpesvirus 8 (HHV-8) infection with multiple clinical subtypes and varying histopathologic patterns. Histologically, many different variants of KS have been reported, yet all can be difficult to recognize and must be differentiated from other vascular tumors. In this report, we studied fourteen cases of a newly described variant of KS reminiscent of a well-differentiated angiosarcoma (angiosarcoma-like KS). All cases showed a diffuse, ill-defined infiltrative dermal-based lesion composed of numerous anastomosing vascular channels of varying caliber lined by a single layer of endothelium with minimal pleomorphism. The vascular proliferation ramified through the dermis and dissected the collagen bundles along with infiltration into the subcutaneous fat and around skin appendages. All cases showed expression of vascular markers (CD31, CD34, and ERG) and were positive for HHV-8. None showed the classic histopathology associated with KS. Without clinical guidance these tumors can be difficult to recognize as KS, creating significant diagnostic challenges. Our study expands on a rare histologic variant of KS that ought to be considered in the differential diagnosis of any cutaneous well-differentiated angiosarcoma. Awareness of this variant of KS is of important for proper diagnosis and management of these patients; thus, careful attention to the histomorphology and clinical history can help lead the pathologist to the correct diagnosis.

Ectodysplasin A (EDA) Signaling: From Skin Appendage to Multiple Diseases.

Ectodysplasin A (EDA) signaling is initially identified as morphogenic signaling regulating the formation of skin appendages including teeth, hair follicles, exocrine glands in mammals, feathers in birds and scales in fish. Gene mutation in EDA signaling causes hypohidrotic ectodermal dysplasia (HED), a congenital hereditary disease with malformation of skin appendages. Interestingly, emerging evidence suggests that EDA and its receptors can modulate the proliferation, apoptosis, differentiation and migration of cancer cells, and thus may regulate tumorigenesis and cancer progression. More recently, as a newly discovered hepatocyte factor, EDA pathway has been demonstrated to be involved in the pathogenesis of nonalcoholic fatty liver disease (NAFLD) and type II diabetes by regulating glucose and lipid metabolism. In this review, we summarize the function of EDA signaling from skin appendage development to multiple other diseases, and discuss the clinical application of recombinant EDA protein as well as other potential targets for disease intervention.

Histopathology spectrum of skin lesions in teaching institution

The skin has many functions and is a complex organ. Epidermis with skin adnexa, melanocytic system, dermis and subcutis are three main anatomic components of skin. Skin diseases are common in developing countries, prevalent among all age groups and up to 2000 skin diseases are known until now. Skin diseases show many different geographical patterns which range from simple vesicular non-neoplastic lesion to fatal neoplastic lesion. Histopathological examination of skin biopsy is necessary for accurate diagnosis, to identify etiological agents and to guide dermatologist or clinician for deciding appropriate management. Present study was carried out to understand prevalence and spectrum of various skin lesion in correlation with age, sex and site of involvement at tertiary care hospital and so to educate community and physicians accordingly after study results. Study Design: Non-interventional, cross-sectional, retrospective study was carried out on all skin biopsies at department of pathology, government medical college Bhavnagar, Gujarat, irrespective of age, sex and clinical diagnosis for Study Duration: from January 2017 to January 2020 for three years. Out of 610 biopsies, Seborrheic keratosis, Leprosy and Basal cell carcinoma were commonly observed non-neoplastic, infective and neoplastic skin lesions, respectively. In our study, most common involved age group is >60 years and male preponderance. Leprosy and Basal cell carcinoma were most commonly observed infective and neoplastic skin lesion in our study respectively. Therefore, community should be educated to prevent airborne droplet transmission and repeated unprotected ultraviolet light sun exposure to reduce the prevalence of both these diseases. We suggest such type of study in different geographical area to plan preventive strategy to reduce morbidity due to various skin lesion.

COVID-19-induced alopecia: a clinical case of diffuse focal alopecia in a patient with generalized pustular psoriasis after a new coronavirus infection

The clinical picture of dermatological diseases in synergy with the pandemic of coronavirus infection demonstrates various, additional, more striking features of the course of dermatoses. The proposed case of observation illustrates the development of diffuse alopecia in a patient with torpid generalized pustular psoriasis, metabolic syndrome, endocrinopathy against the background of a coronavirus infection complicated by polysegmental pneumonia.&#x0D; In the presented clinical observation, the severity of the lesion of the skin and skin appendages correlated with the severity of the course of COVID-19, which was the trigger point of the general pathological process ― immune-mediated T-cell inflammation. In the manifestation of psoriasis and its exacerbation, a significant role was played by viral load and a pronounced comorbid background ― autoimmune thyroid disease and metabolic syndrome. Thus, the severe course of COVID-19 with involvement in the pathological process of the microcirculatory bed, coagulopathy, hypoxia of hair follicles as a result, as well as the reduced estrogenic background of the sixty-one-year-old patient contributed not only to the exacerbation of psoriasis, but also led to diffuse hair loss. The degree of hair loss according to SALT criteria was 82%, which corresponded to a severe degree of lesion. The use of prolonged-acting injectable corticosteroids in the complex treatment of various forms of alopecia was an effective method of therapy in this patient, which is associated with the immunosuppressive effect of corticosteroids in autoimmune damage to hair follicles, a decrease in inflammation of the microvascular bed in various infectious and inflammatory conditions. In the presented case, the high efficiency may also have been associated with the mechanisms of reducing the damaging effect of cytokine inflammatory factors, expressed both with the existing background disease psoriasis and with coronavirus complicated infection.&#x0D; As numerous observations show, COVID-19 is a potential trigger for many dermatological conditions. Examination and treatment of patients with skin pathology infected with COVID-19 requires a systematic integrated approach.

IL-38 orchestrates proliferation and differentiation in human keratinocytes.

Interleukin (IL)-38 is a member of the IL-1 cytokine family with reported anti-inflammatory activity. The highest constitutive IL-38 expression is detected in the skin, where it is mainly produced by differentiating keratinocytes. However, little data are available regarding its biological functions. In this study, we investigated the role of IL-38 in skin physiology. We demonstrate here that dermal fibroblasts and epithelial cells of skin appendages, such as eccrine sweat glands and sebaceous glands, also express IL-38. Next, using two- and three-dimensional cell cultures, we show that endogenous expression of IL-38 correlates with keratinocyte differentiation and its ectopic overexpression inhibits keratinocyte proliferation and enhances differentiation. Accordingly, immunohistochemical analysis revealed downregulation of IL-38 in skin pathologies characterized by keratinocyte hyperproliferation, such as psoriasis and basal or squamous cell carcinoma. Finally, intracellular IL-38 can shuttle between the nucleus and the cytoplasm and its overexpression modulates the activity of the transcription regulators YAP and ID1. Our results indicate that IL-38 can act independently from immune system activation and suggest that it may affect the epidermis directly by decreasing proliferation and promoting differentiation of keratinocytes. These data suggest an important role of keratinocyte-derived IL-38 in skin homeostasis and pathologies characterized by epidermal alterations.

699 An in-vitro keratinocyte model for the evaluation of skin damage induced by 5G radiation

With the rapid spread of next-generation cellular communication technology, wireless bands between 3 – 100 GHz (5G), are increasingly in use in major population centers. The electromagnetic radiation involved remains non-ionizing, however it is of higher energy compared to existing cellular or wi-fi bands; and, this technology’s range is shorter – so that more emitter stations will be needed, placed closer to one another, and thus also closer to the user. This will result in higher net EM energy exposure. There is no clear consensus on the risks inherent in this exposure yet, but there is concern among the public and the scientific community, based on indications that this radiation can affect immune function, trigger inflammatory responses, and influence gene expression linked to protein folding, oxidative stress, tissue / ECM matrix turnover, and more. Further, some skin appendages have been shown to act as antennae for this radiation, which may lead to localized damage. To better understand the effects of this radiation on skin, we irradiated a normal human epidermal keratinocyte culture using a 6 GHz signal generator. Biological effects were evaluated by ELISA or immunostaining. After a remarkably short 1-h exposure time, clear effects were observable in several indicators of keratinocyte function, including: an increase in key inflammatory cytokine IL1-alpha; a reduction in collagenase inhibitor TIMP1; an increase in wound healing and epidermal differentiation facilitator ANGPLT4; and an increase in SA100A9, involved in immune recruitment during injury. These results indicate a clear influence of 5G irradiation on the keratinocytes, suggesting induced changes in skin homeostasis which may be consistent with a state of injury and damage response. In upcoming studies, we hope to be able to show these effects in more depth, and propose some possible solutions for daily users of 5G technology.

767 A biopsy-sized 3D model of skin vascular plexus and appendages enables monitoring T cell trafficking

The human skin vasculature has distinct anatomy with two vascular plexuses and specialized capillary loops near skin appendages and rete ridges, and has diverse functions including thermal regulation and immune cell trafficking. There is currently no engineered 3D skin model to capture this level of complexity. The goal of this study is to generate an anatomically-relevant 3D skin model with five different skin cell types, patterned hair follicles, and a perfusable microvasculature mimicking the superficial vascular plexus of the skin.

LB1013 Nuclear transcriptomics reveals the determinants of eccrine sweat gland fate and differentiation

Eccrine sweat glands are the predominant ectodermal appendage of human skin and are essential in human thermoregulation. Despite their importance, the developmental program and the cellular interactions that drive eccrine gland formation are poorly understood. In mouse volar skin, to which eccrine glands are restricted in this species, the expression of the transcription factor Engrailed-1 (En1) in basal ectoderm is required for the specification of eccrine placodes, while in humans, the upregulation of EN1 in a hallmark of eccrine-forming skin.

LB988 FlowSkin®: A microfluidic human skin model to study pharmacokinetic & biotherapeutic diffusion

Predicting response to biotherapeutics remains a major challenge in the field of bioengineering, especially since the diffusion process of high molecular weight molecules in human tissue remains largely unknown. This study presents an innovative microfluidic system to study the diffusion of therapeutic formulations in ex vivo human skin explants. The FlowSkin® model is composed of a human skin biopsy, which is preserved in a proprietary matrix to keep skin cells and appendages functional, and into which a custom-made porous catheter is implanted.

755 Repurposing of DPP4 inhibition to improve hair follicle activation and regeneration

Injury to the skin results in establishment of fibrosis, which inversely correlates with capacity for regeneration of appendages such as hair follicles (HF). Large wounds on the back of mice can regenerate HF in a central area with reduced expression of fibrosis markers (wound induced hair follicle neogenesis, WIHN), which is facilitated by similar pathways of anagen activation (Wnt, AKT). Identification of modulators of anagen entry and WIHN might aid pinpointing targets for allowing regeneration of skin appendages after trauma or inducing hair growth in individuals affected for example by alopecia.

753 Preferential recruitment of immature neutrophils enables robust skin regeneration

After severe injury, adult mammalian wound healing occurs by formation of fibrotic scar and loss of skin appendages resulting in permanent functional impairment. In mice, severe skin injuries exhibit partial regeneration, including formation of new hair follicles (HFs) in the center of the wound, whereas the periphery remains fibrotic. We previously showed that fibroblasts residing within the regenerative zone exhibit activation of unique transcriptional programs reminiscent of early skin development (Abassi et al, Cell Stem Cell).

Surgical repair for deformities of the nail unit.

The nail apparatus is the largest and most complex skin appendage. Defects in this unit can result in significant functional insufficiency and cosmetic disfigurement. Common nail deformities include split nail, short nail, onycholysis, nail malalignment, hooked nail, and absent nail. Currently, surgical repair is the primary treatment for such deformities. Based on the etiological and anatomical classifications, one or more appropriate operations can be selected to repair nail unit deformities. These include autologous fat grafting, longitudinal cicatrectomy, Z-plasties, nail bed elongation, split-thickness sterile matrix grafting, volar V-Y advanced flap reconstruction, sterile matrix particle grafting, germinal matrix flaps, and germinal matrix grafting. This review discusses the fundamental classification of nail unit deformities, common reconstructive surgical techniques, and their features.

Comparative Spatial Transcriptomic and Single-Cell Analyses of Human Nail Units and Hair Follicles Show Transcriptional Similarities between the Onychodermis and Follicular Dermal Papilla

The nail unit and hair follicle are both hard keratin-producing organs that share various biological features. In this study, we used digital spatial profiling and single-cell RNA sequencing to define a spatially resolved expression profile of the human nail unit and hair follicle. Our approach showed the presence of a nail-specific mesenchymal population called onychofibroblasts within the onychodermis. Onychodermis and follicular dermal papilla both expressed Wnt and bone morphogenetic protein signaling molecules. In addition, nail matrix epithelium and hair matrix showed very similar expressions profile, including the expression of hard keratins and HOXC13, a transcriptional regulator of the hair shaft. Integration of single-cell RNA sequencing and digital spatial profiling data through computational deconvolution methods estimated epithelial and mesenchymal cell abundance in the nail- and hair-specific regions of interest and revealed close transcriptional similarity between these major skin appendages. To analyze the function of bone morphogenetic proteins in nail differentiation, we treated cultured human nail matrix keratinocytes with BMP5, which are highly expressed by onychofibroblasts. We observed increased expressions of hard keratin and its regulator genes such as HOXC13. Collectively, our data suggest that onychodermis is the counterpart of dermal papilla and that BMP5 in onychofibroblasts plays a key role in the differentiation of nail matrix keratinocytes.

Matrixyl Patch vs Matrixyl Cream: A Comparative In Vivo Investigation of Matrixyl (MTI) Effect on Wound Healing.

Wound healing is one of the most complex biological processes. Studies show that Matrixyl (MTI), known as a cosmetic peptide, can lead to a faster healing process. The contribution of MTI to collagen formation during wound healing also depends on its mode of delivery and its release over time. Here, we investigate two modes of MTI-delivery system, the influence of MTI patch for wound healing application in comparison with MTI cream. In this study, animals were randomly divided into seven groups and studied for 21 days: patches containing two different concentrations of MTI (P-MTI-0.1 mg and P-MTI-1 mg), a cream containing MTI (C-MTI-1 mg), a patch (P-MTI-0), a cream with no MTI (C-MTI-0), a positive control (Comfeel), and a negative control (sham) group. To study the wound healing process, the change in collagen density, angiogenesis, epitheliogenesis, histopathology, immunohistochemical analysis, and wound area through imaging was monitored and measured. The macroscopic results showed that wound healing was improved from 63.5 up to 81.81% in treatment groups compared to that in the negative control group (P < 0.05 and P < 0.001). In addition, C-MTI-1 and P-MTI-1 had a larger impact on wound healing compared to that in the positive control group (Comfeel, P < 0.05). In hematoxylin and eosin (H&E) staining analysis, the rejuvenation of skin appendage was visible in both groups of cream and patches with MTI. According to the obtained results, the re-epithelialization had a higher range for the patch with MTI in comparison with cream containing MTI and positive control.

Skin conditions among pediatric dermatology outpatients in Botswana

An understanding of the prevalence patterns of skin diseases in children in Botswana is needed to guide national dermatological policy development, training, and resource allocation to improve patient care. To describe local skin disease patterns in children aged 0-18 years presenting for dermatologic care in Botswana. A retrospective review of records from 1st January 2011 to 31st December 2016 was conducted at the outpatient dermatology clinic of Princess Marina Hospital (PMH) in Gaborone, Botswana and outreach clinic sites. There were 4413 pediatric visits constituting 18.6% of all dermatology visits. There was a slight male predominance of 1.2:1. The majority of disorders were noninfectious 80.1% (3537/4413) versus infectious 14.6% (645/4413), with 5.2% (231/4413) unclassified. In the noninfectious category, two-thirds were inflammatory, followed by disorders of nails, skin appendages, and pigmentary disorders. Atopic dermatitis was the most common inflammatory disorder. Over half of infectious skin diseases were viral, followed by fungal and bacterial disorders. In the HIV-related disorders, the majority were verrucae 94% (108/115) followed by Kaposi sarcoma. The nine most common skin diagnoses accounted for close to 70% of all skin diseases seen at the clinic, and these included atopic dermatitis (almost half of all cases), followed by verruca, acne, and vitiligo. There is a high burden of skin disorders in children in Botswana. In our cohort, a small number of skin conditions made up the vast majority of pediatric diagnoses. This information can be used to guide dermatology training and resource allocation to better manage these common diseases.

Effects of testosterone on skin structure and factors related to androgen conversion and binding in Hetian sheep.

The effects of androgens on human skin mainly include the regulation of growth and differentiation of hair follicles and sebaceous glands. Androgens may have some physiological roles in sheep skin that are similar to those of humans, but further confirmation is needed. Therefore, Hetian sheep were chosen in this study as an animal model to explore the effects of testosterone on skin structure and factors related to androgen conversion and binding in Hetian sheep. The sheep were treated with different concentrations of testosterone for 42days. Skin tissue sections were prepared and then subjected to hematoxylin-eosin, Sacpic, Masson's trichrome, and Oil Red O staining to observe changes in skin morphology. Changes in the content of blood-related factors were also detected using ELISA kits. The skin tissue distribution of androgen receptor was explored by immunohistochemistry and immunofluorescence assays. The results showed that testosterone significantly increases the sebaceous gland area and stimulates the formation of new sebaceous glands. Further exploration revealed that testosterone promotes the proliferation of sebaceous gland juvenile cells. However, testosterone was found to have no significant effect on hair follicle density and hair follicle structure. Testosterone increased dihydrotestosterone levels but decreased 5α-reductase 1 and 5α-reductase 2 levels. The androgen receptors were distributed in the hair follicles, sebaceous glands, and some major skin appendages of Hetian sheep. This study suggests that androgens can be effective in regulating sebum production in sheep. This study will help advance research efforts to further explore the molecular and cellular mechanisms by which androgens modify sheep follicles and sebaceous glands.

Fibroblast Growth Factor 7 Suppresses Fibrosis and Promotes Epithelialization during Wound Healing in Mouse Fetuses.

Adult mammalian wounds leave visible scars, whereas skin wounds in developing mouse fetuses are scarless until a certain point in development when complete regeneration occurs, including the structure of the dermis and skin appendages. Analysis of the molecular mechanisms at this transition will provide clues for achieving scarless wound healing. The fibroblast growth factor (FGF) family is a key regulator of inflammation and fibrosis during wound healing. We aimed to determine the expression and role of FGF family members in fetal wound healing. ICR mouse fetuses were surgically wounded at embryonic day 13 (E13), E15, and E17. Expression of FGF family members and FGF receptor (FGFR) in tissue samples from these fetuses was evaluated using in situ hybridization and reverse transcription-quantitative polymerase chain reaction. Fgfr1 was downregulated in E15 and E17 wounds, and its ligand Fgf7 was upregulated in E13 and downregulated in E15 and E17. Recombinant FGF7 administration in E15 wounds suppressed fibrosis and promoted epithelialization at the wound site. Therefore, the expression level of Fgf7 may correlate with scar formation in late mouse embryos, and external administration of FGF7 may represent a therapeutic option to suppress fibrosis and reduce scarring.