Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Skin”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 865 records · Page 48Linked to original sources
PubMed1999

Effect of topical local anesthetic application to skin harvest sites for pain management in burn patients undergoing skin-grafting procedures.

OBJECTIVE: To determine if topical administration of local anesthesia, applied to fresh skin-harvest sites, reduces pain and analgesic requirements after surgery. SUMMARY BACKGROUND DATA: Nonopioid treatments for pain after therapeutic procedures on patients with burns have become popular because of the side effects associated with narcotics. The topical administration of local anesthesia originally offered little advantage because of poor epidermal penetration. METHODS: This study compares 2% lidocaine with 0.5% bupivacaine or saline, topically applied after skin harvest, to determine what effect this may have on pain and narcotic use. Sixty patients with partial- or full-thickness burns to approximately 10% to 15% of their body were randomly divided into three groups: group 1 received normal saline, group 2 had 0.5% bupivacaine, and group 3 had 2% lidocaine sprayed onto areas immediately after skin harvest. Blood samples were subsequently obtained to measure concentrations of the local anesthetic. Hemodynamic variables after surgery, wake-up times, emetic symptoms, pain, and narcotic use were compared. RESULTS: Higher heart rates were noted in the placebo group than in those receiving lidocaine or bupivacaine. No differences were noted in recovery from anesthesia or emetic symptoms. Pain scores were lower and 24-hour narcotic use was less in patients who received lidocaine. Plasma lidocaine levels were greater than bupivacaine at all time points measured. CONCLUSIONS: Topical lidocaine applied to skin-harvest sites produced an analgesic effect that reduced narcotic requirements compared with patients who received bupivacaine or placebo. Local anesthetic solutions aerosolized onto skin-harvest sites did not affect healing or produce toxic blood concentrations.

Adolescent↗
PubMed2004

Meshed unexpanded split-thickness skin grafting for reconstruction of penile skin loss.

PURPOSE: Sheets of unmeshed, split-thickness skin grafts (STSGs) have been advocated in potent men with penile skin deficiency. Since the survival of sheet grafts is rarely 100% and the appearance of unexpanded 1:1 mesh grafts is quite good, we used this technique. We report our experience with meshed, unexpanded STSGs for all penile resurfacing regardless of erectile function. MATERIALS AND METHODS: Nine consecutive patients with penile skin loss were prospectively treated between March 2001 and January 2003 with meshed STSGs to the penis. The underlying condition was Fournier's gangrene in 4 cases, chronic lymphedema in 2, skin deficiency from prior surgeries in 2 and Crohn's disease in 1. Graft thickness was 0.012 or 0.016 inches and meshing was performed in a 1:1 ratio. Meshed slits were oriented transversely without expansion and the graft juncture was located on the ventral surface in zigzag fashion. Graft take, appearance, and sexual and voiding function were assessed postoperatively. RESULTS: All 9 patients had 100% graft take. At a mean followup of 6 months a satisfactory cosmetic outcome was documented photographically in all except 1 case involving chronic penile manipulation. Erectile function and ejaculation were preserved in potent patients. CONCLUSIONS: Unexpanded meshed STSGs of penile skin loss yielded satisfactory functional and cosmetic outcomes.

Adult↗
PubMed1996

Topical retinaldehyde increases skin content of retinoic acid and exerts biologic activity in mouse skin.

Retinaldehyde, a natural metabolite of beta-carotene and retinol, has been proposed recently for topical use in humans. Because retinaldehyde does not bind to retinoid nuclear receptors, its biologic activity should result from enzymatic transformation by epidermal keratinocytes into ligands for these receptors, such as all-trans retinoic acid and 9-cis-retinoic acid. In this study, we analyzed by high performance liquid chromatography the type and amounts of tissue retinoids as well as several biologic activities resulting from topical application of either retinaldehyde or all-trans retinoic acid on mouse tail skin. Biologic activities of all-trans retinoic acid and retinaldehyde were qualitatively identical in metaplastic parameters (induction of orthokeratosis, reduction of keratin 65-kDa mRNA, increase in filaggrin and loricrin mRNAs) and hyperplastic parameters (increase in epidermal thickness, increase in bromodeoxyuridine (BrdU)-positive cells, increase in keratin 50-kDa mRNA, and reduction in keratin 70-kDa mRNA). Some quantitative differences, not all in favor of all-trans retinoic acid, were found in several indices. Cellular retinoic acid-binding protein II and cellular retinol-binding protein I mRNAs were increased by both topical retinaldehyde and all-trans retinoic acid. Whereas all-trans retinoic acid, 9-cis-retinoic acid, and 13-cis-retinoic acid were not detectable (limit 5 ng/g) in vehicle-treated skin, 0.05% retinaldehyde-treated skin contained 13 +/- 6.9 ng/g wet tissue of all-trans retinoic acid (mean +/- SD), 12.6 +/- 5.9 ng/g 13-cis-retinoic acid, and no 9-cis-retinoic acid. In contrast, 9-cis-retinoic acid was detectable in 0.05% of all-trans retinoic acid-treated skin, which also contained 25-fold more all-trans retinoic acid and 5-fold more 13-cis-retinoic acid than retinaldehyde-treated skin. Our results show that topical retinaldehyde is transformed in vivo into all-trans retinoic acid by mouse epidermis. The small amounts of ligand for retinoic acid nuclear receptors thus produced are sufficient to induce biologic effects similar to those resulting from the topical application of the ligand itself in much higher concentration.

Administration, Topical↗
PubMed1987

Effect of skin pretreatment with vehicle alone or drug in vehicle on flux of a subsequently applied drug: results of hairless mouse skin and diffusion cell studies.

Clinical and in vitro evidence suggest that pretreatment of skin with a drug or vehicle can influence topical drug delivery. In this study, hairless mouse skin in diffusion cells was treated for 48 h with topical applications of vehicle alone (oleic acid (OA), isopropyl myristate, octanol (OCT), dimethylformamide, propylene glycol (PG), ethylene glycol (EG), formamide), or mixtures of OA and PG, or with 5-fluorouracil (5-FU) suspensions in each of these vehicles. Twenty-four hours after removing the initially applied agent, a standard suspension of theophylline in PG was applied to the skin surface and the flux of theophylline was determined over the next 48 h. Skin pretreatment with vehicle alone increased theophylline flux 1.6-(EG) to 122-fold (OCT) over control experiments in which the skins were not pretreated. Pretreatment with nonpolar vehicles with lower solubility parameters (OA, OCT, or mixed vehicles containing one of these) had the greatest effect on subsequent theophylline flux. Pretreatment with 5-FU in various vehicles caused a subsequent increased theophylline flux similar to the effect of vehicle alone, except for pretreatment with 5-FU in vehicles which did not have much effect themselves. In those instances, theophylline fluxes up to 16-fold over the effect of those vehicles alone were observed.

Animals↗
PubMed1982

Vitamin A in human skin: II Concentrations of carotene, retinol and dehydroretinol in various components of normal skin.

Pro-vitamin A(beta-carotene) and the predominant forms of vitamin A in human skin (retinol and dehydroretinol) were analyzed in hydrolyzed specimens from 4 cadavers and 22 healthy subjects. Beta-carotene was identified in extracts of epidermis by its specific absorption spectrum. Vitamin A was determined by high-pressure liquid chromatography. The concentrations were related to the wet weight or protein content of the sample. The analysis of different skin compartments showed that the concentrations of the 3 constituents were usually related as follows: carotene greater than retinol greater than dehydroretinol. The concentrations were always higher in the epidermis than in the upper dermis. Skin surface lipids contained carotene and retinol but not in amounts sufficient to contribute to the higher epidermal values. Analysis of epidermal autopsies from 5 different skin areas (back, breast, arm, leg and foot) and of epidermal biopsies from the back of the healthy subjects showed that the interindividual differences were larger for carotene and dehydroretinol than for retinol, whereas the intraindividual variations were larger for retinol. The mean (+/- SD) concentrations of carotene, retinol and dehydroretinol in back skin epidermis of healthy subjects were 13 +/- 5, 1.7 +/- 0.4 and 0.4 +/- 0.2 microgram/g protein, respectively. No significant variations with age and sex were found.

Carotenoids↗
PubMed1992

Differential modulation of bFGF receptors by TGF-beta in adult skin, scleroderma skin, and newborn foreskin fibroblasts.

Effects of transforming growth factor beta (TGF-beta) on proliferative responses to basic fibroblast growth factor (bFGF) were studied in human diploid fibroblasts cell strains derived from three different sources: adult skin, scleroderma, and newborn foreskin. All three types of cell strains were similarly responsive to TGF-beta, whereas adult skin fibroblasts were significantly more responsive to bFGF. Incubation of cells with TGF-beta prior to bFGF addition substantially increased responsiveness of adult skin fibroblasts to this latter cytokine, slightly increased that of scleroderma fibroblasts, and decreased that of foreskin fibroblasts. Modulation of bFGF receptors by TGF-beta correlated positively with these mitogenic effects. Adult skin fibroblasts showed increases of both high- and low-affinity receptors and scleroderma fibroblasts showed small increases of high-affinity receptors only, whereas foreskin fibroblasts showed no changes. Heparitinase treatment of adult skin fibroblasts during TGF-beta pre-incubation resulted in reduced bFGF binding to low-affinity receptors and reduced mitogenic response to bFGF, suggesting that the TGF-beta-stimulated increase of low-affinity receptors in these cells contributes to the observed enhanced mitogenic effects of bFGF. Abnormal responses of scleroderma fibroblasts to TGF-beta/bFGF stimulation, particularly failure to synthesize low-affinity receptors in response to TGF-beta, adds a new characteristic to the fibrotic phenotype of scleroderma fibroblasts.

Adult↗
PubMed2004

Lysyl oxidase-like and lysyl oxidase are present in the dermis and epidermis of a skin equivalent and in human skin and are associated to elastic fibers.

Elastic fiber formation involves the secretion of tropoelastin which is converted to insoluble elastin by cross-linking, initiated by the oxidative deamination of lysine residues by lysyl oxidase. Five lysyl oxidase genes have been discovered. This study deals with the expression of two isoforms, LOX and LOX-like (LOXL), in human foreskin and in a human skin-equivalent (SE) model that allows the formation of elastic fibers. In this model, keratinocytes are added to a dermal equivalent made of fibroblasts grown on a chitosan-cross-linked collagen-GAG matrix. LOX and LOXL were detected by immunohistochemistry in the dermis and the epidermis of both normal skin and in a SE. This expression was confirmed by in situ hybridization on the SE. LOX and LOXL expression patterns were confirmed in human skin. The ultrastructural localization of LOXL was indicative of its association with elastin-positive materials within the SE and human skin, though interaction with collagen could not be discarded. LOX was found on collagen fibers and could be associated with elastin-positive materials in the SE and human skin. LOXL and LOX were detected in keratinocytes where LOX was mainly expressed by differentiating keratinocytes, in contrast to LOXL that can be found in both proliferating and differentiating fibroblasts. These data favor a role for LOXL in elastic fiber formation, together with LOX, and within the epidermis where both enzymes should play a role in post-translational modification of yet unknown substrates.

Amino Acid Oxidoreductases↗
PubMed1994

Extracellular matrix derived from hair and skin fibroblasts stimulates human skin melanocyte tyrosinase activity.

There is indirect evidence that both skin and hair melanocytes are regulated by the activity of adjacent cells. In hair, the specialized fibroblasts (dermal papilla cells) appear to play a role in the regulation of hair growth. Hair pigmentation may relate to hair growth. In skin, melanocytes are located adjacent to the basement membrane zone. As far as we are aware, direct interactions of fibroblasts with melanocytes have not previously been investigated. Accordingly, the objective of this study was to develop co-culture conditions in which to investigate whether dermal fibroblasts from skin or hair could influence melanocyte differentiation. The influence of fibroblast-conditioned media, co-culture with fibroblasts, and fibroblast-derived extracellular matrix (ECM) on normal human skin melanocyte tyrosinase activity was examined. Fibroblasts from both skin and hair were capable of altering melanocyte morphology and significantly increasing tyrosinase activity when melanocytes were cultured in the absence, but not the presence, of the major proliferative drives. Although stimulation of tyrosinase activity was detectable with conditioned medium and co-culture with fibroblasts, the most striking result was obtained with the fibroblast-produced ECM which, on average, produced a four-fold increase in tyrosinase activity within 6 days. Thus, the study describes co-culture conditions in which the stimulatory effect of the fibroblast on melanocyte differentiation can be examined.

Cell Differentiation↗
PubMed2003

Epidemiology of cutaneous melanoma and non-melanoma skin cancer in Schleswig-Holstein, Germany: incidence, clinical subtypes, tumour stages and localization (epidemiology of skin cancer).

BACKGROUND: Population-based figures on skin cancer are essential for a realistic assessment of the personal disease burden, prevention modes and the need for caring. The Robert Koch Institute in Germany estimates the incidence of melanoma skin cancer as seven cases in 100 000 persons (age-standardized by the European standard rate). Population-based studies presumably show higher incidence rates of 10-16 cases in 100 000 persons. Few data exist for non-melanoma skin cancer (NMSC) as this is not systematically registered in Germany. OBJECTIVES: To present the first population-based results from the Schleswig-Holstein (Germany) Cancer Registry on incidence, stage distribution, clinical types and localization of skin cancer and to compare the results with other studies. METHODS: The Cancer Registry of the Bundesland Schleswig-Holstein with 3500 registering institutions, 100 of which are dermatological institutions, investigates all notifiable incident cancer cases according to international standards. From the recorded data all melanoma and NMSC cases were identified and evaluated. RESULTS: Between 1998 and 2001, 1784 malignant melanoma (MM) and 12 956 NMSC cases underwent diagnostic and analytical evaluation. For MM, age-standardized incidence rates were 12.3 and 14.8 in 100 000 men and women, respectively, and the mean age of men was greater than that of women (56.6 vs. 54.9 years, P < 0.05). Superficial spreading melanoma was the most frequent clinical type (39.1%). The tumours were predominantly located on the trunk in men (46.8%) in contrast to leg and hip in women (39.5%). For NMSC, the age-standardized incidence rates were 100.2 and 72.6 in 100 000 men and women, respectively. More than 80% of all tumours were basal cell carcinoma. CONCLUSIONS: The first population-based data from Schleswig-Holstein on the characteristics (age, sex, histological subtypes, localization and stage) of skin tumours agree well with the existing literature and may thus be regarded as representative. However, markedly higher incidences for MM and NMSC in the north of Germany compared with other parts of the country were observed. As the incidence rates from the north of Germany fit well into the European geographical pattern, we assume no regional increase. Therefore, the official German estimates on cutaneous tumours may largely depend on regional factors and may not be regarded as representative for all regions in Germany.

Adolescent↗
PubMed2005

Multiple tissue kallikrein mRNA and protein expression in normal skin and skin diseases.

BACKGROUND: Human tissue kallikreins are a gene family (KLK1-KLK15) encoding for 15 secretory serine proteases (hK1-hK15). Two tissue kallikrein proteins, hK5 and hK7, were previously found in the stratum corneum (SC), stratum granulosum (SG) and appendages. hK8 was also shown to be secreted via lamellar granules and numerous KLK mRNAs were previously identified. KLKs are believed to be responsible for desquamation of corneocytes and sebum, sweat and hair maturation. OBJECTIVES: To demonstrate immunohistochemically the expression of hK6, hK8 and hK13 in normal skin tissue and to show an increased cell number expressing kallikrein mRNAs and proteins in psoriasis vulgaris (PV) and atopic dermatitis (AD). METHODS: Samples of normal, PV and AD skin were obtained. hK6-, hK8- and hK13-specific antibodies were produced and used for immunohistochemical analysis. Multiple KLK mRNAs were synthesized and used for in situ hybridization study. RESULTS: Three other hKs, namely hK6, hK8 and hK13, were immunohistochemically identified as new skin serine proteases in the whole SC, SG, sebaceous glands, eccrine sweat glands, hair follicles and nerves. We also demonstrated an increased number of cells expressing KLK mRNAs and hKs in PV and AD. In PV, KLK mRNAs/hKs were predominantly expressed in the upper epidermis. In AD, hK distribution was rather diffuse and expanded into the lower epidermis. CONCLUSIONS: The colocalization of various hKs seems to be essential for the regulation of serine protease activity in skin and for steady desquamation and skin barrier function. Moreover, the increased number of cells expressing multiple KLK mRNA and hK in PV and AD could be a clue to elucidate their pathogenesis.

Adult↗
PubMed2005

Scarring skin lesions of discoid lupus erythematosus are characterized by high numbers of skin-homing cytotoxic lymphocytes associated with strong expression of the type I interferon-induced protein MxA.

BACKGROUND: Infiltrating T lymphocytes are considered to play a major pathological role in skin lesions of cutaneous lupus erythematosus (CLE), a cutaneous autoimmune disease of unknown aetiology. Earlier histological studies revealed that the inflammatory infiltrate in CLE skin lesions is predominantly composed of T lymphocytes, with a slight predominance of CD4+ over CD8+ T cells, but failed to explain the development of scarring skin lesions, characteristic for chronic discoid lupus erythematosus (CDLE). Because recent investigations have highlighted the relevance of cytotoxic lymphocytes in autoimmune tissue destruction, we hypothesized that the scarring CDLE lesions might be caused by cytotoxic T lymphocytes. OBJECTIVES: To analyse skin biopsies of 15 patients with CLE [10 female, five male; localized CDLE (lCDLE), n = 5; disseminated CDLE (dCDLE), n = 5, subacute CLE (SCLE), n = 5] and five control biopsies taken from healthy controls and to characterize the inflammatory infiltrate. Methods We used immunohistochemistry, including staining for the cytotoxic molecule granzyme B, the skin-homing molecule cutaneous lymphocyte antigen (CLA) and the protein MxA, which is specifically induced by type I interferons (IFNs). RESULTS: We found a strong coexpression of granzyme B and CLA on lesional lymphocytes of patients with scarring lCDLE and dCDLE, which was significantly enhanced when compared with nonscarring SCLE and healthy controls. The increased expression of granzyme B was closely associated with the lesional expression of the type I IFN-induced protein MxA. CONCLUSIONS: Our results provide evidence that type I IFNs and potentially autoreactive cytotoxic lymphocytes targeting adnexal structures are highly associated with scarring lupus erythematosus lesions and might be responsible for their scarring character.

Biopsy↗
PubMed1989

The effect of anorexia nervosa on skin thickness, skin collagen and bone density.

The effects of anorexia nervosa on skin thickness, skin collagen content and bone density were investigated in a cross-sectional study of 36 women with anorexia nervosa with a 4-year median duration of amenorrhoea and compared with a group of 33 women of comparable age without anorexia and with normal periods. The median skin thickness, assessed radiologically, was significantly reduced (P less than 0.01) from 0.88 mm in the comparison group to 0.70 mm in the anorectic group and the median collagen content was significantly reduced from 209 micrograms/mm2 in the comparison group to 164 micrograms/mm2 in the anorectic group (P less than 0.05). The median bone density in the comparison group was 0.93 gHA/cm2 at the lumbar spine and 0.84 gHA/cm2 at the proximal femur. These values were greatly reduced in the women with anorexia nervosa to 0.77 gHA/cm2 and 0.65 gHA/cm2 respectively (P less than 0.01). Our findings confirm the loss of bone mass with anorexia and demonstrate the coexistent loss of skin thickness and skin collagen content. This association supports the hypothesis that a generalized loss of collagen is a major factor in the causation of osteoporosis following oestrogen deficiency.

Adolescent↗
PubMed1983

Assessment of skin irritancy: measurement of skin fold thickness.

It is desirable to use more objective methods than visual scoring for the assessment of skin irritancy reactions. The edema, or fluid accumulation in the exposed skin sites, can be accurately measured by a caliper and this alternative method of assessment is evaluated from different aspects. Sodium lauryl sulfate (SLS) and non-anoic acid in different concentrations were applied daily to human and animal (rabbit and guinea pig) skin, and a dose-response relationship established. Higher concentrations of the irritants induced an earlier response. With 5% SLS as the test substance and the increase in skin fold thickness as the single parameter of skin irritancy, the guinea pig was found to be less reactive than rabbit and man. Measurement techniques, reproducibility and advantages and disadvantages with different animal models are discussed.

Animals↗
PubMed1996

Unusual wrinkle formation after temporary skin fixation followed by UVB irradiation in hairless mouse skin.

Generally, many wrinkles form on the human face, and temporary wrinkles eventually become permanent. We evaluated the effects of temporary skin fixation on wrinkle formation after UVB irradiation using the back skin of hairless mice. In the group treated with UVB irradiation immediately after production using cyanoacrylate resin of an artificial groove parallel to the midline, wrinkles formed parallel to the midline, an uncommon direction for wrinkle formation in this mouse model. These wrinkles did not disappear even when the skin was stretched. No such changes were observed in the group in which only the temporary groove alone was produced without UVB irradiation. In 3-D surface parameter analysis, all roughness parameters in the group treated with UVB irradiation immediately after production of an artificial groove were significantly increased relative to the age-matched control group. In contrast, no differences were observed between the group in which only the temporary groove alone was produced without UVB irradiation and age-matched controls. The results of this study suggest that both a temporary groove in the skin and UVB irradiation are necessary for wrinkle formation in the back skin of hairless mice.

Animals↗
PubMed2006

Towards the development of a pragmatic technique for isolating and differentiating nestin-positive cells from human scalp skin into neuronal and glial cell populations: generating neurons from human skin?

Nestin+ hair follicle-associated cells of murine skin can be isolated and differentiated in vitro into neuronal and glial cells. Therefore, we have asked whether human skin also contains nestin+ cells, and whether these can be differentiated in vitro into neuronal and/or glial cell populations. In this methodological pilot study, we show that both are indeed the case - employing purposely only very simple techniques for isolating, propagating, and differentiating nestin+ cells from normal human scalp skin and its appendages that do not require selective microdissection and tissue compartment isolation prior to cell culture. We show that, it is in principle, possible to maintain and propagate human skin nestin+ cells for extended passage numbers and to differentiate them into both neuronal (i.e. neurofilament+ and/or PGP9.5+) and glial (i.e. GFAP+, MBP+ and/or O4+) cell populations. Therefore, human scalp skin can serve as a highly accessible, abundant, and convenient source for autologous adult stem cell-like cells that offer themselves to be exploited for neuroregenerative medicine purposes.

Cell Differentiation↗
PubMed1969

A study of the mechanism of water transfer across frog skin by a comparison of the permeability of the skin to deuterated and tritiated water.

1. Frog abdominal skins were placed between the two half-cells of a modified version of Ussing's frog skin apparatus.2. The rate of equilibration of deuterated and tritiated water across the skin was followed at pH 5.0, 6.9, and 8.0 with Ringer solution bathing both surfaces of the skin; and at pH 7.0 with sulphate Ringer solution bathing both surfaces of the skin.3. The ratio of the permeability coefficients for the influx of deuterated and tritiated water had a mean value over all the experiments of 0.9954 +/- 0.0207, n = 27, indicating that no isotope effect was observable within the limits of accuracy of the experimental method.4. The thickness of the unstirred layers associated with the frog skin was measured, and, from the data obtained, values of the true permeability coefficients for each isotope were calculated.

Abdomen↗
PubMed1977

Adherence pharyngeal and skin strains of group A streptococci to human skin and oral epithelial cells.

Group A streptococci isolated from skin adhere in greater numbers to human skin epithelial cells than to cells obtained from buccal mucosa whereas streptococci isolated from a throat tend to adhere in greater numbers to buccal epithelial cells than to skin epithelial cells in vitro. M protein-producing strains of group A streptococci did not adhere in significantly greater numbers than M-negative strains. Lipoteichoic acid inhibited binding of streptococci to skin epithelial cells as well as was previously shown for oral epithelial cells. Our results suggest that lipoteichoic acid is more centrally involved than M protein in binding streptococci to skin and mucosal surfaces.

Adhesiveness↗
PubMed2006

Insulin-like growth factor 1 receptor signaling regulates skin development and inhibits skin keratinocyte differentiation.

The insulin-like growth factor 1 receptor (IGF-1R) is a multifunctional receptor that mediates signals for cell proliferation, differentiation, and survival. Genetic experiments showed that IGF-1R inactivation in skin results in a disrupted epidermis. However, because IGF-1R-null mice die at birth, it is difficult to study the effects of IGF-1R on skin. By using a combined approach of conditional gene ablation and a three-dimensional organotypic model, we demonstrate that IGF-1R-deficient skin cocultures show abnormal maturation and differentiation patterns. Furthermore, IGF-1R-null keratinocytes exhibit accelerated differentiation and decreased proliferation. Investigating the signaling pathway downstream of IGF-1R reveals that insulin receptor substrate 2 (IRS-2) overexpression compensates for the lack of IGF-1R, whereas IRS-1 overexpression does not. We also demonstrate that phosphatidylinositol 3-kinase and extracellular signal-regulated kinase 1 and 2 are involved in the regulation of skin keratinocyte differentiation and take some part in mediating the inhibitory signal of IGF-1R on differentiation. In addition, we show that mammalian target of rapamycin plays a specific role in mediating IGF-1R impedance of action on keratinocyte differentiation. In conclusion, these results reveal that IGF-1R plays an inhibitory role in the regulation of skin development and differentiation.

Animals↗