尖锐湿疣组织中TGFβ1,TGFβRⅡ及Cyclin E的表达

目的研究转化生长因子β1(TGFβ1)、转化生长因子βⅡ型受体(TGFβRⅡ)和细胞周期素E(Cyclin E)蛋白在尖锐湿疣(CA)组织中的表达。方法采用免疫组织化学SP法和图像分析系统检测30例CA患者皮损、15例正常人皮肤(包皮)组织中TGFβ1,TGFβRⅡ及Cyclin E表达及分布。结果(1)TGFβ1,CyclinE在CA组织中的表达(分别为0.26380±0.01965,0.29554±0.01650)均显著高于正常皮肤组织(分别为0.20088±0.03815,0.24330±0.06417,P<0.05);TGFβRⅡ在CA组织中的表达(0.09730±0.01760)显著低于正常皮肤组织(0.23407±0.04883,P<0.05);(2)TGFβ1与Cyclin E在CA组织中的表达呈正相关(P<0.05);而TGFβRⅡ与Cyclin E在CA组织中的表达呈负相关(P<0.05)。结论CA组织中TGFβ1表达上调,而TGFβRⅡ表达下调,使TGFβ信号传导通路受阻,致TGFβ1缺乏对细胞增殖负性调节作用,导致Cyclin E过表达使细胞周期调控异常,细胞增殖。     

尖锐湿疣组织内血管内皮生长因子和转化生长因子-α表达北大核心CSCD

目的探讨血管内皮生长因子（VEGF）和转化生长因子-α（TGF-α）在尖锐湿疣（CA）血管形成中的作用。方法用RT—PCR和免疫组化法检测30例CA和15例正常包皮中VEGF、TGF-α和CD34表达。结果CA中VEGF和TGF—dmRNA表达明显高于正常包皮（P〈0．001）;CA中VEGF、TGF-α蛋白阳性表达率分别为90％、86．7％,正常包皮中则为40％、26．7％,二者的差异具有统计学意义（P〈0．01）。CA中微血管密度比正常包皮明显增多（P〈0．01）,且CA中VEGF、TGF-α蛋白表达与MVD呈显著正相关（P〈0．01）。结论CA中VEGF和TGF-α表达上调,可能促进血管生成,参与CA的发生、发展。     

血管内皮细胞生长因子在尖锐湿疣皮损中的表达

目的　通过对尖锐湿疣 (CA)皮损中血管内皮细胞生长因子 (VEGF)表达的研究 ,探讨VEGF在CA发病、发展和复发中的作用。方法　采用免疫组化方法检测CA皮损组织及正常包皮组织中VEGF的表达水平。结果　在正常对照包皮组织中VEGF无或有弱的表达 ,在CA皮损组织则呈强阳性表达。结论　VEGF可能参与了CA皮损的发生和发展。     

尖锐湿疣组织中TGFβI、TGFβRII及cyclin E的表达

目的:检测转化生长因子βI(TGFβI)、转化生长因子β II受体(TGFβRII)和细胞周期素E(cyclin E)蛋白在尖锐湿疣(CA)组织中的表达.方法:采用免疫组化SP法和图像分析系统检测30例CA患者皮损,15名正常人皮肤(包皮)组织中TGFβI、TGFβRII及cyclin E的表达.结果:TGFβI和cyclin E在CA组织中的表达均显著高于正常皮肤组织(P<0.05);TGFβRII在CA组织中的表达显著低于正常皮肤组织(P<0.05);TGFβI与cyclin E在CA组织中的表达呈正相关(P<0.05);TGFβRII与cyclin E在CA组织中的表达呈负相关(P<0.05).结论:TGFβRII表达下调,使TGFβ信号传导通路受阻,降低了TGFβI对cyclin E表达的抑制作用,及其对细胞增殖的负性调节作用,使CA组织过度增殖,可能是CA发病机制之一.     

GluT1 mRNA和VEGF mRNA在尖锐湿疣组织中的表达

目的探讨葡萄糖转运蛋白1(GluT1)mRNA和血管内皮生长因子(VEGF)mRNA在尖锐湿疣(CA)发病中的作用。方法采用原位杂交技术检测40例CA组织中GluT1 mRNA和VEGF mRNA的表达,并与20例正常包皮组织作对照。结果 CA组织中GluT1和VEGF mRNA阳性表达率分别为90.00%(36/40),95.00%(38/40),正常对照组分别为25.00%(5/20),90.00%(18/20);CA组织中GluT1 mRNA阳性表达强度多为(2+)～(3+),正常对照组多在(-)～(2+)。CA组织中VEGF mRNA阳性表达强度多为(2+)～(3+),正常对照组多在(+)～(2+)。GluT1 mRNA阳性表达率及表达强度与正常对照组比较差异具有统计学意义(P均<0.05);VEGF mRNA阳性表达率与正常对照组比较差异无统计学意义(P>0.05),但VEGF mRNA表达强度与正常对照组比较差异具有统计学意义(P<0.05)。CA组织中GluT1和VEGF mRNA表达呈正相关(r=0.332,P=0.036)。结论尖锐湿疣组织中存在GluT1和VEGF mRNA过表达,GluT1和VEGF mRNA可能在CA能量代谢和血管生成中发挥一定作用。     

尖锐湿疣组织中HIF-1α,VEGF的表达及其与血管生成的关系

目的探讨尖锐湿疣(CA)组织中HIF-1α,VEGF的表达及其与血管生成的关系。方法采用免疫组化法检测30例CA标本和20例正常包皮组织中HIF-1α和VEGF的表达,并用CD34标记血管内皮细胞计数微血管密度(MVD)。结果 CA组织中HIF-1α,VEGF的表达均显著高于正常对照组(P<0.01);CA组织中HIF-1α与VEGF的表达呈正相关(r=0.87,P<0.01);CA组织中MVD明显高于正常对照组(P<0.01);HIF-1α,VEGF的表达与CA组织中MVD均呈正相关(P均<0.01)。结论 HIF-1α和VEGF在CA组织中过度表达,二者可能通过促进血管生成参与CA的发病。     

尖锐湿疣损害中转化生长因子α、β1的表达

目的：探讨TGF－α、β1在尖锐湿疣（CA）发病机制中的作用。方法：免疫免疫组化SP法检测30例CA损害中TGF－α、β1的原位表达，并以20例健康男性正常包皮组织作为对照。结果：两组TGF－α、β1表达率均相同；CA组TGF－α、β1表达阳性者中的表达程度分别显著高于对照组（P＜0．001）；其过度表达率也分别明显高于对照组（P＜0．005）。结论：CA组织细胞可合成及分泌较多的TGF－α、β1，作为中间介质在CA发病中发挥致细胞增生的作用。     

环氧合酶-2和血管内皮生长因子mRNA在皮肤鳞状细胞癌组织中的表达

目的 探讨环氧合酶-2(COX-2)、血管内皮生长因子(VEGF)mRNA在皮肤鳞状细胞癌(SCC)和正常人皮肤组织中的表达以及它们之间相互关系。方法 应用逆转录-聚合酶链反应(RT-PCR)方法,检测24例SCC和10例正常人皮肤组织中COX-2和VEGF mRNA的表达。结果 RT-PCR结果显示,在正常人皮肤组织中COX-2和VEGF mRNA呈较弱表达或无表达,吸光度平均值分别为(0.01±0.01)和(0.02±0.02);有79.2%(19/24)SCC组织中COX-2 mRNA表达水平增高,平均值为(0.56±0.48),与正常皮肤组织比较差异有统计学意义(P<0.05);VEGF mRNA在SCC组织中全部高表达(24/ 24,100%),平均值为(0.66±0.35),与正常人皮肤组织比较差异有统计学意义(P<0.05)。经相关性分析两者之间的表达呈明显正相关(r=0.86)。结论 COX-2可能与SCC血管形成有关,且其作用可能通过上调VEGF通道来发挥作用。     

血管内皮生长因子、增殖细胞核抗原在尖锐湿疣中的表达

目的探讨尖锐湿疣(CA)组织中血管内皮生长因子(VEGF)、增殖细胞核抗原(PCNA)的表达及相关性。方法采用免疫组化SP法检测32例CA组织和10例正常人皮肤组织中VEGF,PCNA的表达,并做相关性分析。结果 CA组织中VEGF,PCNA表达水平均明显高于正常人皮肤组织(P0.001)。CA组织中VEGF和PCNA的表达模式具有相同性:以基底层、棘层细胞表达最为显著,为二者共同的优势表达部位;二者的表达呈正相关关系。结论 CA组织中均存在VEGF和PCNA的过度表达,二者表达存在正相关性关系,表明表皮角质细胞过度增殖引起的局部缺氧是刺激VEGF过度表达的重要原因。     

尖锐湿疣中蛋白酶激活受体-1表达与血管增生的关系及意义

目的:探讨尖锐湿疣(CA)组织中蛋白酶激活受体(protease-activated receptor,PAR)-1的表达与血管生成的关系及意义.方法:对28例CA患者病变组织行常规组织病理切片和苏木精-伊红染色,并对其进行血管计数,应用反转录(RT)-PCR和免疫组化法检测PAR-1的表达情况.同时以17份正常包皮组织作为对照.结果:CA皮损组织的血管数比正常包皮组织明显增多t=5.192,P＜0.001);CA皮损组织中PAR-1 mRNA平均表达水平显著高于正常包皮组织(t=7.26,P＜0.001);PAR-1蛋白在CA组织中的表达较正常包皮组织显著增强(x2=16.218,P＜0.001),PAR-1在CA皮损中从基底层至角质层下方均有表达,而正常包皮仅在基底层有弱阳性表达.且PAR-1蛋白表达与血管数存在显著正相关r=0.823,P＜0.001).结论:PAR-1在CA皮损组织中的过度表达以及与血管数的正相关提示PAR-1与血管生成有关,PAR-1在CA发病中起一定的作用.     

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.     

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.     

Insulin-like growth factor 1 and hair growth

Insulin-like growth factor 1 (IGF-1) has been identified as an important growth factor in many biological systems.[1] It shares considerable structural homology with insulin and exerts insulin-like effects on food intake and glucose metabolism. Recently it has been suggested to play a role in regulating cellular proliferation and migration during the development of hair follicles. [2,3] To exert its biological effects, the IGF-1 is required to activate cells by binding to specific cell-surface receptors. The type I IGF receptor (IGF-1R) is the only IGF receptor to have IGF-mediated signaling functions.[1] In circulation, this growth factor mediates endocrine action of growth hormone (GH) on somatic growth and is bound to specific binding proteins (BPs). The latter control IGF transport, efflux from vascular compartments and association with cell surface receptors.[4] In tissues, IGF-1 is produced by mesenchymal type cells and acts in a paracrine and autocrine fashion by binding to the IGF-1R. This binding activates the receptor tyrosine kinase (RTK) that triggers the downstream responses and finally stimulates cell division.[5] IGF-1 may therefore be able to stimulate the proliferation of hair follicle cells through cellular signaling pathways of its receptors. Local infusion of IGF-1 into sheep has been reported to be capable of stimulating protein synthesis in the skin.[6] It may also increase the production of wool keratin. Recently, transgenic mice overexpressing IGF-1 in the skin have been shown to have earlier hair follicle development than controls.[7] In addition, this growth factor plays an important role in many cell types as a survival factor to prevent cell death.[8] This anti-apoptotic function of IGF-1 may be important to the development of follicle cells as follicles undergo a growth cycle where the regressive, catagen phase is apoptosis driven. In this review, the effects of IGF-1 on follicle cell proliferation and differentiation are discussed. In particular, the paracrine versus endocrine action of IGF-1 on hair growth and the targeting of expression of the growth factor to the follicles of transgenic animals will be emphasized. The anti-apoptotic role of IGF-1 in hair follicles is also reviewed. Prospects for future studies on hair and fiber growth by IGF-1 are discussed.     

The effect of hepatocyte growth factor/scatter factor on human hair follicle growth

The effect of hepatocyte growth factor/scatter factor (HGF/SF) on human hair follicle growth was examined using a serum-free organ culture system. The DNA synthesis in human hair follicles and elongation of the hair shaft were measured subsequent to the follicle isolation and culture at 31 °C in 95% O₂-5% CO₂ for 72 h. Results showed that HGF/SF significantly increased ³H-thymidine (P < 0.001) incorporation and hair follicle length (P < 0.05). The effect of HGF/SF was dose-dependent with a maximal stimulation at 10 ng/ml.     

Immunohistochemical analysis of keratinocyte growth factor and fibroblast growth factor 10 expression in psoriasis

The pathogenic mechanism underlying the hyperproliferation of keratinocytes in psoriasis is still not completely clarified. The production of cytokines released by activated T lymphocytes infiltrating the upper dermis probably has a crucial role. Even dermal fibroblasts can participate in the process through the secretion of growth factors, and some studies have reported an increased expression of the insulin-like growth factor 1. Few studies, however, have focused on the possible involvement of the keratinocyte growth factor (KGF/FGF-7) and the fibroblast growth factor 10 (FGF-10/KGF-2), which are secreted by fibroblasts and stimulate keratinocyte proliferation acting through a receptor specifically expressed by epithelial cells. The aim of this study was to investigate the expression of KGF and FGF-10 on the skin of patients with psoriasis by immunohistochemical analysis and to evaluate the correlation with the lymphocyte infiltrate and the epidermal proliferation. Immunostaining for KGF and FGF-10 showed that both the growth factors are upregulated in the upper dermis of psoriatic skin, and that the expression is correlated with the presence of T-cell infiltrate and with keratinocyte proliferation. Our data suggest that in psoriatic lesions activated lymphocytes can stimulate fibroblasts to produce KGF and FGF-10, which in turn contribute to sustain the hyperproliferative status of the keratinocytes.     

Trans retinoic acid enhances the growth response of epidermal keratinocytes to epidermal growth factor and transforming growth factor beta

Retinoids have been shown to either stimulate or inhibit epidermal keratinocyte proliferation. We have observed that in serum and growth factor free medium (basal medium), epidermal growth factor (EGF) and transforming growth factor alpha (TGF alpha) stimulated DNA synthesis in mouse epidermal keratinocyte cultures (mKC) in a time- and dose-dependent manner. Incubation with all-trans retinoic acid (RA) greatly enhanced the stimulatory effect of EGF. Transforming growth factor beta (TGF beta) inhibited the EGF-induced DNA synthesis in a dose-dependent manner, and the inhibition was greatly enhanced by a low dose of RA. Treatment of growth-factor deprived human keratinocyte cultures (hKC) with RA before incubation in basal medium containing EGF or a mixture of EGF, bovine pituitary extract (BPE), and insulin caused a dose-related increase in DNA synthesis and cell growth (cell number), respectively. A low concentration of RA also enhanced the inhibitory effect of TGF beta on growth-factor-induced DNA synthesis and cell growth in hKC. These findings suggest that the differential effects of retinoids on epidermal keratinocyte proliferation are in part due to an enhancement of the response of keratinocytes to positive and negative peptide growth factors.