血管内皮生长因子受体家族在HaCaT细胞中的表达

目的 探讨血管内皮生长因子受体(VEGFR)家族在角质形成细胞系HaCaT细胞的表达。方法 RT-PCR法检测HaCaT细胞中VEGFR家族中VEGFR-1、VEGFR-2、VEGFR-3及neuropilin (NRP)-1、NRP-2的mRNA表达,蛋白免疫印迹法检测VEGFR家族蛋白质的表达,同时免疫荧光法定位VEGFR家族在HaCaT细胞中的表达情况。结果 RT-PCR发现VEGFR-1、VEGFR-2、VEGFR-3及NRP-1、NRP-2 mRNA在HaCaT细胞中均有表达;蛋白免疫印迹发现VEGFR-1、VEGFR-2、VEGFR-3蛋白质相对分子质量均为180 000,NRP-1、NRP-2为140 000。HaCaT细胞膜及细胞质内检测到较强的VEGFR家族荧光信号,以细胞膜表达为强。结论 在mRNA及蛋白质水平,HaCaT细胞均表达VEGFR-1、VEGFR-2、VEGFR-3及NRP-1、NRP-2。     

Expression of Fc receptors for IgG during acute and chronic cutaneous inflammation in atopic dermatitis

Atopic dermatitis is an allergic skin disease characterized by elevated total and antigen-specific serum IgE and IgG4 levels. In acute and chronic cutaneous inflammation, large cellular infiltrates including T cells, dendritic cells and macrophages are found, especially in the dermis. These cells play an important part in the regulation of local inflammatory reactions. Receptors binding IgG (FcgammaR) are involved in dendritic cell and macrophage function. In this study, we examined the in vivo distribution and cellular expression of the three classes of leucocyte FcgammaR in human skin during acute and chronic cutaneous inflammation in atopic dermatitis. Atopy patch test skin was used as a model for acute inflammation in atopic dermatitis, while chronic lesional skin was used to investigate FcgammaR expression in chronically inflamed skin. In atopy patch test sites no increase in the number of CD1a+ dendritic cells and a slight increase in macrophages compared with non-lesional skin was observed. Our results showed increased expression of FcgammaRI (CD64) and FcgammaRIII (CD16) in acutely inflamed skin as well as in chronically inflamed lesional skin, compared with healthy and non-lesional atopic dermatitis skin. FcgammaRI was expressed by RFD1+, RFD7+ and CD68+, but not by CD1a+ dermal dendritic cells. RFD1+ dendritic cells and CD68+ macrophages were the main FcgammaRIII-expressing cells during the acute inflammatory reaction. The significant increase in expression of FcgammaRIII (CD16) and FcgammaRI (CD64) probably results from upregulation of the receptors on resident cells. Insight into the presence of FcgammaR+ cells in human skin during inflammation is important both for our understanding of skin immune reactions and the development of new therapeutic concepts.     

Nerve growth and expression of receptors for nerve growth factor in tumors of melanocyte origin.

Nerve growth factor (NGF) stimulates growth and differentiation of sensory and sympathetic neurons. It is not known what role NGF plays in melanoma development, but nevus and malignant melanoma cells express NGF-receptor (NGF-R). We counted nerve fibers within melanocytic nevi, primary cutaneous melanomas, and cutaneous melanoma metastases using a monoclonal antibody (MoAb) as marker against a 200-kD glycoprotein that is expressed on human nerves. The expression of NGF-R was studied in serial cryostat sections using a MoAb against the NGF-R. Compared to normal skin, increased numbers of nerve fibers were found in 72 melanocytic nevi. In congenital nevi their number significantly increased with age. In 47 primary cutaneous melanomas the number of nerve fibers decreased in proportion to tumor thickness. In 33 cutaneous melanoma metastases no accumulation of nerve fibers was found. NGF-R was not expressed in normal skin melanocytes and in the majority of nevus cells in melanocytic nevi. Considerable numbers of NGF-R-positive nervus cells were found only in some congenital nevi and few acquired nevi with dysplastic features. By contrast, in primary and metastatic melanomas higher expression of NGF-R was observed. The increased number of nerve fibers in melanocytic nevi suggests that neurite-promoting factors are produced in situ. Production of such factors appears to be lost in malignant melanoma cells. The finding of an inverse correlation between an abundance of nerve fibers in NGF-R-poor nevi and a high expression of NGF-R in melanomas that show no evidence of nerve growth suggest a role of NGF and its receptor in malignant melanocytic tumors.     

Keratinocyte growth factor receptors

Modulation of the number of functional growth factor receptors on the epithelial cell surface that is exposed to the action of cognate ligands represents a key strategy in cellular physiology to regulate the proliferation rate and the differentiation process. The keratinocyte growth factor receptor (KGFR) and the epidermal growth factor receptor (EGFR), among the growth factor receptors expressed on keratinocytes, are believed to play a unique crucial role in controlling epithelial proliferation. KGFR and EGFR appear to also contribute to the cell differentiation process. Modulation of KGFR and EGFR on the proliferation rate and differentiation process has been reported either in in vivo or in vitro conditions. This article reviews the architecture, the ligand binding activated-signaling pathways, and the biologic effects of KGFR and EGFR on keratinocytes.     

Expression of stem cell factor in cutaneous mastocytosis

Stem cell factor has recently been identified as a potent growth factor for bone marrow stem cells, melanocytes and mast cells. In order to evaluate its possible role in human mastocytosis, skin lesions from 13 patients with urticaria pigmentosa and five patients with mastocytomas, and normal skin specimens from five healthy donors were studied by immunohistochemistry, using polyclonal and monoclonal (hkl-12) antibodies against stem cell factor, and a monoclonal antibody (YB5.B8) against its receptor, the c-kit proto-oncogene product. Stem cell factor expression was noted in all sections studied, with an equal distribution pattern for both antibodies, but a weaker intensity with the hkl-12 reagent. Cytoplasmic staining was noted in keratinocytes, Langerhans cells, sweat gland ductal lining cells, mast cells, endothelial cells and spindle-shaped dermal stromal cells. An intense, diffusely granular reaction pattern was noted in all cells, except for a sparse, coarsely granular pattern in mast cells and stromal cells. In urticaria pigmentosa, staining was weaker in keratinocytes, but more prominent in Langerhans cells. In all sections, toluidine blue-positive mast cells and TA 99-positive basal epidermal melanocytes were the only cells to react with the c-kit antibody. Mastocytomas and urticaria pigmentosa lesions thus exhibit different patterns of stem cell factor expression. However, a possible pathogenetic role of this factor in mastocytosis remains to be determined.     

Expression of mast cell growth modulating and chemotactic factors and their receptors in human cutaneous scars

In order to explore possible mechanisms involved in the previously documented turnover of mast cell subpopulations in human cutaneous scars, we have examined selected factors known to stimulate and/or modulate mast cell hyperplasia (SCF, NGF, TGFbeta1, GM-CSF) and their receptors in human cutaneous scar tissue. On immunohistochemistry, numbers of SCF- and TGFbeta1-positive cells were significantly increased in the epidermis and throughout the dermis in scars (n = 27) of varying ages (4-369 d old), compared with normal skin (n = 12). Furthermore, TRbetaRI, II, and the NGF-p75 receptors were significantly increased in the epidermis, TRbetaRI and NGF-TrkA throughout the dermis, and TRbetaRII, NGF-p75, and GM-CSFR only in the mid- and lower dermis of scars. NGF and GM-CSF expression was in contrast scarce and weak, with no differences between normal skin and scars. In tissue extracts, mRNA levels of SCF, TGFbeta1, TRbetaI and II, and both NGF-receptors, but not GM-CSFR, were significantly increased as well. TRbetaI and II were identified in up to 90% and 83%, respectively, of isolated normal skin mast cells on flow cytometry, and GM-CSFR and NGFR-p75 were identified on 70% and 73%, respectively, of avidin-positive normal mast cells on double immunofluorescence microscopy. As described before for the SCF receptor KIT, GM-CSFR and NGFR-p75 were partly or entirely downregulated on avidin-positive mast cells in scars. The marked upregulation of TGFbeta1, its type I and II receptors, and SCF suggest that these factors play a major role in the orchestration of mast cell increase in human cutaneous scars whereas the role of NGF and GM-CSF is less clear, despite the significant upregulation of their receptors.     

Increased nerve growth factor and its receptors in atopic dermatitis: an immunohistochemical study

Evidence suggests that neurotrophins may regulate certain immune functions and inflammation. In the present study, the localization and distribution of nerve growth factor (NGF) and its receptors were explored using immunohistochemical methods, with the aim of detecting the cause of the neurohyperplasia in early lesions of atopic dermatitis (AD). In AD involved skin, strong NGF-immunoreactive (IR) cells were observed in the epidermis. In some cases, a huge number of infiltrating cells with stronger NGF immunoreactivity was seen mainly in the dermal papillae. Some trkA immunoreactivity was observed in the outer membrane of cells in the basal and spinal layers of the epidermis. In the papillary dermis, a larger number of cells demonstrated strong trkA immunoreactivity. The p75 NGFr-IR nerve fibre profiles were increased (900 per mm²; p<0.001) compared to normal [the involved skin also differed from the uninvolved skin (p<0.05)] in the dermal papillae. These nerve fibres were larger, coarser and branched, some of them terminated at p75 NGFr-IR basal cells, and also revealed a stronger fluorescence staining than the controls or the uninvolved skin. In normal healthy volunteers and AD uninvolved skin, the NGF immunoreactivity was weak in the basal layer of epidermis. Only a few trkA positive cells were seen in the basal layer of the epidermis and upper dermis. The IR epidermal basal cells revealed a striking patchy arrangement with strong p75 NGFr immunostaining in the peripheral part of the cells, and short and thick NGFr-IR nerve fibre profiles appeared as smooth endings scattered in the dermis including the cutaneous accessory organs. Using NGF and p75 NGFr double staining, both immunoreactivities showed a weak staining in the epidermis and dermis in normal and uninvolved skin. In the involved dermis of AD, the intensity of p75 NGFr-IR nerves was stronger in areas where there were also increased numbers of NGF-IR cells. These findings indicate that NGF and its receptors may contribute to the neurohyperplasia of AD.     

The role of chronic inflammation in cutaneous fibrosis: fibroblast growth factor receptor deficiency in keratinocytes as an example

Fibrosis is associated with a variety of skin diseases and causes severe aesthetic and functional impairments. Functional studies in rodents, together with clinical observations, strongly suggest a crucial role of chronic injury and inflammation in the pathogenesis of fibrotic diseases. The phenotype of mice lacking fibroblast growth factor (FGF) receptors 1 and 2 in keratinocytes supports this concept. In these mice, a defect in keratinocytes alone initiated an inflammatory response, which in turn caused keratinocyte hyperproliferation and dermal fibrosis. As the mechanism underlying this phenotype, we identified a loss of FGF-induced expression of claudins and occludin, which caused abnormalities in tight junctions with concomitant deficits in epidermal barrier function. This resulted in severe transepidermal water loss and skin dryness. In turn, activation of keratinocytes and epidermal γδ T cells occurred, which produced IL-1 family member 8 and S100A8 and S100A9. These cytokines attracted immune cells and activated fibroblasts, resulting in a double paracrine loop through production of keratinocyte mitogens by dermal cells. In addition, a profibrotic response was induced in fibroblasts. Our results highlight the importance of an intact epidermal barrier for the prevention of inflammation and fibrosis and the role of chronic inflammation in the pathogenesis of fibrotic diseases.     

Expression and function of keratinocyte growth factor and activin in skin morphogenesis and cutaneous wound repair

Reepithelialization and granulation tissue formation during cutaneous wound repair are mediated by a wide variety of growth and differentiation factors. Recent studies from our laboratory provided evidence for an important role of keratinocyte growth factor (KGF) in the repair of the injured epithelium and for a novel function of the transforming growth factor-beta superfamily member activin in granulation tissue formation. KGF is weakly expressed in human skin, but is strongly upregulated in dermal fibroblasts after skin injury. Its binding to a transmembrane receptor on keratinocytes induces proliferation and migration of these cells. Furthermore, KGF has been shown to protect epithelial cells from the toxic effects of reactive oxygen species. We have identified a series of KGF-regulated genes that are likely to play a role in these processes. In addition to KGF, activin seems to be a novel player in wound healing. Activin expression is hardly detectable in nonwounded skin, but this factor is highly expressed in redifferentiating keratinocytes of the hyperproliferative wound epithelium as well as in cells of the granulation tissue. To gain insight into the role of activin in wound repair, we generated transgenic mice that overexpress activin in basal keratinocytes of the epidermis. These mice were characterized by a hyperthickened epidermis and by dermal fibrosis. Most importantly, overexpression of activin strongly enhanced the process of granulation tissue formation, demonstrating a novel and important role of activin in cutaneous wound repair.     

Notch信号相关受体/配体在皮肤恶性黑素瘤中的表达

目的 检测Notch信号通路中Notch1、Notch4、Jagged1以及Dll4在皮肤恶性黑素瘤组织中的表达,初步探讨Notch信号通路在黑素瘤发病机制中的作用.方法 免疫组化SP法检测40例恶性黑素瘤及15例色素痣石蜡标本中Noteh1、Notch4、Jagged1以及Dll4的表达模式和表达强度.采用SPSS21.0软件进行卡方检验及Spearman秩相关分析.结果 在40例黑素瘤组织(31例阳性表达)及15例色素痣组织(3例阳性表达)Notch1的表达率差异有统计学意义(x2=15.281,P=0.000),原位(18例)及侵袭性黑素瘤(22例)间Notch1表达强度差异无统计学意义(x2=0.631,P=0.427).Notch4、Jagged1以及Dll4的表达率在恶性黑素瘤与色素痣之间差异均有统计学意义(均P＜0.05),三者表达强度在原位与侵袭性黑素瘤之间差异亦均有统计学意义(P＜0.05).在黑素瘤组织中,Notch1与Jagged1的表达呈正相关(rs=0.350,P=0.027),与Dll4的表达亦呈正相关(rs=0.562,P=0.000),但是Jagged1与Dll4的表达呈负相关(rs=-0.734,P=0.000).结论 Notch信号通路异常可能是黑素瘤的发病机制之一,但具体作用机制有待进一步研究.     

Expression of nerve growth factor mRNA and its translation products in the anagen hair follicle

The cellular localization of NGF mRNA and its translation products have been identified in ovine hair follicles. NGF mRNA was detected in the proliferating cells of the follicle bulb and differentiating cells of the suprabulbar region, but was absent from the outer root sheath. Western analysis revealed the presence of a 73 kDa NGF prohormone in extracts of ovine flank skin, but the mature 13 kDa NGF was absent. Immunohistochemical analysis with antibodies specific to mouse NGF and a pro-NGF specific domain localized the NGF prohormone to outer root sheath cells in the upper bulb region of the follicle, adjacent to the zone of keratinization. Antibody binding was also associated with the luminal epithelium of the apocrine sweat gland and the pilary canal of the follicle at its junction with the epidermis. These observations, together with the reported presence of high- and low-affinity NGF receptors in the follicle, implicate the NGF prohormone-responsive neuronal system in the regulation of hair growth.     

Autocrine nerve growth factor in human keratinocytes

Biologically active nerve growth factor (NGF) is synthesised and released by proliferating normal human keratinocytes. NGF up-regulates the expression of NGF mRNA in keratinocytes. Keratinocytes express both the low (p75)- and the high-affinity (TrkA) NGF-receptors, which are located in the basal layer of the epidermis. K252, a specific inhibitor of trk phosphorylation, blocks NGF-induced keratinocyte proliferation, in absence of exogenous NGF. Normal keratinocytes over-expressing TrkA proliferate better than control transfectants, while the NGF mimicking anti-Trk antibody induces an increased keratinocyte proliferation in Trk over-expressing cells as compared to mock transfected keratinocytes. In addition, NGF over-expressing keratinocytes proliferate better than mock transfected cells. K252, by blocking TrkA phosphorylation, induces apoptosis in normal keratinocytes, but not in keratinocytes over-expressing bcl-2. Furthermore, NGF transfected keratinocytes are protected from UV-B-induced keratinocyte apoptosis, by maintaining constant levels of Bcl-2 and Bcl-xL . Taken together these results support the concept of an autocrine survival system sustained by NGF and its high-affinity receptor in human keratinocytes. Because NGF and Trk levels are highly expressed in psoriasis. one could speculate that NGF autocrine system plays a role in the mechanisms associated with this and other hyperproliferative skin conditions, including cancer.     

Expression and localization of thymidine phosphorylase/platelet-derived endothelial cell growth factor in skin and cutaneous tumors

Thymidine phosphorylase/platelet-derived endothelial cell growth factor (TPase/PD-ECGF) is a catabolic enzyme that has been shown to be chemotactic for endothelial cells in vitro and angiogenic in vivo. TPase/PD-ECGF expression is increased in a variety of tumors. In the skin, TPase is active in normal keratinocytes in vitro and in vivo. Our objective was to study the expression and localization of TPase/PD-ECGF by immunohistochemical analysis in normal skin and cutaneous tumors and to correlate this information with enzymatic activity of TPase. TPase/PD-ECGF expression was observed in keratinocytes with intense staining of the infundibulum of hair follicles but no staining of hair bulbs. Expression localized primarily to the nucleus of keratinocytes in the basal layer but was more intense and cytoplasrmic in suprabasal keratinocytes. Increased expression of TPase/PD-ECGF in differentiated cells was confirmed by in vitro studies of TPase activity. In cutaneous tumors, there was positive staining for TPase/ PD-ECGF in squamous cell carcinomas (10/10), eccrine poromas (3/4), eccrine syringomas (4/4), trichoepitheliomas (1/3), and tumors of the follicular infundibulum (2/3) and melanomas (5/8). There was no staining of any intradermal nevi (0/2), basal cell carcinomas (0/10) or Merkel cell carcinoma (0/1). We conclude TPase/PD-ECGF is found throughout the epidermis and its expression increases with differentiation of keratinocytes. In cutaneous tumors, expression of TPase/PD-ECGF may be linked to the cell of origin of the tumor as well as the tumor's degree of differentiation.     

Epidermal growth factor/transforming growth factor alpha receptors and psoriasis

The abnormal growth and differentiation in psoriasis is reflected in the abnormal regulation of Epidermal Growth Factor/Transforming Growth Factor Alpha (EGF/TGF alpha) receptor metabolism. In psoriasis and other hyperproliferative skin conditions these receptors are persistently expressed throughout the interfollicular epidermis as long as the growth stimulatory signal persists. One of the first biochemical signs of effective therapy of psoriasis is the return of the EGF/TGF alpha receptor pattern toward the primarily basilar distribution seen in normal human adult skin. Whether the abnormal expression of TGF alpha in the involved skin induces the persistent expression of EGF receptors is not known nor is the signal that causes the increased production of TGF alpha. Studies to determine what factors regulate EGF receptor expression and TGF alpha induction may yield important new insights into the pathogenesis and therapy of psoriasis.     

Circulating vascular endothelial growth factor in cutaneous malignant melanoma

BACKGROUND: Angiogenesis has been reported as a parameter of potential prognostic value in solid tumours, as it may facilitate tumour growth and metastasis. One of the most important growth factors involved in angiogenesis is vascular endothelial growth factor (VEGF). OBJECTIVES: To determine the predictive value of circulating VEGF levels in a cohort of patients with melanoma. METHODS: In a prospective cohort study, 324 patients with cutaneous melanoma at different clinical stages were investigated over 2 years (2002-04). VEGF was measured in plasma using enzyme-linked immunosorbent assay. Two hundred and eight patients were able to be followed up for progression of their disease and for blood sample collection (mean +/- SD follow-up 13.4 +/- 0.8 months). Data were compared with the extent of the disease and the clinical course. RESULTS: A significant increase in plasma VEGF levels was found in patients with melanoma compared with healthy controls, with statistically significant differences between patients in stages I, II and III vs. those in stage IV, but not between patients in stages I, II and III. When considering the 237 patients in stages I and II, no statistical correlation was found between plasma VEGF levels and tumour thickness. Baseline plasma VEGF levels were not significantly higher in patients who relapsed compared with nonprogressing patients. Among the 35 patients (two stage I, eight stage II and 25 stage III) who experienced a progression during follow-up, an increase in plasma VEGF level to > 100 pg mL(-1) was found in 20 (sensitivity 57.1%), while 38 of the 173 remaining nonprogressing patients demonstrated an increase in VEGF level, indicating a specificity of 78%. In addition, an increase in plasma VEGF level was found in 58 patients during follow-up, of whom 20 showed evidence of progression, indicating a positive predictive value of 34.5%. However, among the 150 remaining patients who did not demonstrate any increase in plasma VEGF level during follow-up, only 15 experienced a progression, indicating a negative predictive value of 90%. CONCLUSIONS: Our data confirm that blood VEGF levels are significantly increased in patients with melanoma and, more interestingly, that the absence of plasma VEGF level increase during follow-up appears to be associated with remission.     

Expression of the soluble vascular endothelial growth factor receptor-1 in cutaneous melanoma: role in tumour progression

Background Vascular endothelial growth factor (VEGF)‐A, placenta growth factor (PlGF) and their corresponding membrane receptors are involved in autocrine and paracrine regulation of melanoma growth and metastasis. Besides the membrane receptors, a soluble form of the VEGF receptor (VEGFR)‐1 (sVEGFR‐1) has been identified, that behaves both as a decoy receptor, sequestering VEGF‐A and PlGF, and as an extracellular matrix (ECM) molecule, promoting endothelial cell adhesion and migration through the interaction with α5β1 integrin. Objectives To analyse whether sVEGFR‐1 plays a role during melanoma progression. Methods sVEGFR‐1 expression was evaluated in a panel of 36 melanoma cell lines and 11 primary human melanocyte cultures by quantitative real‐time polymerase chain reaction analysis and in specimens of primary or metastatic melanoma lesions from 23 patients by immunohistochemical analysis. Results sVEGFR‐1 expression was highly upregulated in melanoma cell lines with respect to human melanocytes. Interestingly, cell lines obtained from cutaneous metastases showed a significant reduction of sVEGFR‐1 expression, as compared with cell lines derived from primary tumours. These results were confirmed by immunohistochemical analysis of sections from primary skin melanomas and the corresponding cutaneous metastases, suggesting that modulation of sVEGFR‐1 expression influences ECM invasion by melanoma cells and metastasis localization. Moreover, we provide evidence that adhesion of melanoma cells to sVEGFR‐1 is favoured by the activation of a VEGF‐A/VEGFR‐2 autocrine loop. Conclusions Our data strongly suggest that sVEGFR‐1 plays a role in melanoma progression and that low sVEGFR‐1/VEGF‐A and sVEGFR‐1/transmembrane VEGFR‐1 ratios might predict a poor outcome in patients with melanoma.     

Contiguous cutaneous inflammation

BACKGROUND: Contiguous cutaneous inflammation is a circumscribed inflammatory reaction of the skin overlying a pathological process affecting an adjacent deep-seated anatomical structure. Contiguous cutaneous inflammation can sometimes reveal serious internal diseases. Through a case report and a literature review, we characterize the concept of contiguous cutaneous inflammation. CASE REPORT: A 77-year-old woman with a past medical history of rhinorrhoea and chronic headache was admitted for a verrucous and erythematous lesion on her right cheek, evolving for two months with incomplete remission after numerous antibiotics. Histopathological examination was inconclusive. Facial CT revealed pansinusitis. Diagnosis of contiguous cutaneous inflammation to sinusitis was retained. Complete healing of cutaneous lesions was observed after surgical treatment of the sinusitis. DISCUSSION: Contiguous cutaneous inflammation is characterized by localization over the causal disease, parallel evolution with the latter and the absence of clinicopathological specificity. The underlying pathological process is variable and may be tumoral or infectious, or simply the presence of an internal device. Migration of inflammatory cells and/or diffusion of mediators in a localized skin area could be involved in pathogenesis.     

尖锐湿疣中转化生长因子β受体、受体活化Smad和共有Smad的表达

目的 探讨尖锐湿疣中转化生长因子β（TGF-β）信号转导途径TGFβ受体（TGFβR）、受体活化Smad和共有Smad蛋白的表达情况。方法 采用EliVisionTMplus免疫组织化学技术分别检测20例尖锐湿疣和15例正常人对照皮肤中TGFβRⅠ、TGFβRⅡ、Smad1/2/3、磷酸化Smad2/3（p-Smad2/3）和Smad4的表达。结果 TGFβRⅠ、TGFβRⅡ、Smad1/2/3、p-Smad2/3和Smad4在对照正常人皮肤的表皮中均有表达。尖锐湿疣表皮中TGFβRⅠ、TGFβRⅡ、Smad1/2/3、p-Smad2/3和Smad4的免疫组化染色强度均明显低于对照正常人皮肤的表皮（P < 0.05或P < 0.01）。结论 尖锐湿疣表皮中存在着TGFβR、受体活化Smad和共有Smad蛋白的表达下调或缺失，可干扰TGFβ信号向下游的转导。失去TGFβ抑制作用的表皮角质形成细胞可出现异常增殖，导致尖锐湿疣表皮过度增殖病理改变的形成。     

神经生长因子受体P75和P140trkAmRNA在寻常型银屑病患者皮损中的表达

目的研究神经生长因子(nerve growth factor,NGF)受体P75和P140trkA在寻常型银屑病发病机制中的作用.方法应用原位杂交技术检测了33例寻常型银屑病患者(18例为进展期,15例为静止期)和10例正常人皮肤组织中两受体(P75和P140trkA)mRNA的表达情况.结果与正常人皮肤比较,寻常型银屑病皮损及非皮损中P75和P140trkA受体mRNA的表达明显上调,且皮损中的表达明显高于非皮损区(P＜0.01);进展期患者皮损与非皮损中P75和P140trkA受体mRNA的表达分别高于静止期患者的皮损与非皮损区(P＜0.01).结论神经生长因子及其两受体可能是参与银屑病病理机制的重要因子.