HIF-1α蛋白在烧伤后增生性瘢痕组织中的表达及临床意义
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摘要
目的:探讨烧伤后瘢痕增生患者组织中HIF-1α蛋白的表达水平及其临床意义。方法:选取82例烧伤后瘢痕增生患者的增生性瘢痕组织作为实验组,同时取其自身正常皮肤组织为对照组。采用荧光定量PCR检测HIF-1α的mRNA表达水平;采用免疫组化检测HIF-1α的蛋白表达水平;采用Westernblot检测HIF-1α相关细胞因子,转化生长因子β(TGF-β)、E-钙黏蛋白(E-cadherin)及血管内皮生长因子(VEGF)的蛋白表达水平。结果:与正常组织(0.29±0.03)相比,增生性瘢痕组织中HIF-1α的mRNA相对表达水平(1.45±0.16)显著增高,差异有统计学意义(P<0.05);免疫组化显示,与正常组织中HIF-1α的阳性表达率(8.54%)相比,增生性瘢痕组织中HIF-1α的阳性表达率(70.7%)显著升高(P<0.05);Western blot显示,与正常组织相比,增生性瘢痕组织中HIF-1α、TGF-β及VEGF蛋白表达水平显著增加,E-cadherin蛋白表达水平显著下降,差异有统计学意义(P<0.05)。结论:HIF-1α在增生性瘢痕组织中高表达,并通过调控下游细胞因子TGF-β、VEGF及E-cadherin的表达参与增生性瘢痕的发生、发展。
Objective To investigate the expression and clinical significance of HIF-1 α protein in burn scar hyperplasia.Methods The hyperplastic scar tissue of 82 patients with scar hyperplasia after burn was selected as experimental group, and its normal skin tissue was taken as control group. The HIF-1α mRNA expression level was detection by real-time PCR. The protein expression of HIF-1α was analyzed by immunohistochemistry. The expression of HIF-1α-related cytokines TGF-β, E-cadherin and VEGF were detected by Western blot. Results Compared with normal tissues(0.29±0.03), the mRNA relative expression of HIF-1α in hypertrophic scar tissue(1.45±0.16)was significantly increased(P<0.05). Immunohistochemistry showed that the positive expression of HIF-1α in hypertrophic scar tissue(70.7%) was significantly higher than that in normal tissues(8.54%,P<0.05). Western blot showed that compared with normal tissues, the expression of HIF-1α, TGF-β and VEGF in hypertrophic scar tissue were significantly increased, whereas the expression level of E-cadherin was significantly decreased(P <0.05). Conclusion HIF-1α was highly expressed in hypertrophic scar tissue and participates in the development of hypertrophic scar by regulating the expression of downstream cytokines TGF-β, VEGF and E-cadherin.
Objective To investigate the expression and clinical significance of HIF-1 α protein in burn scar hyperplasia.Methods The hyperplastic scar tissue of 82 patients with scar hyperplasia after burn was selected as experimental group, and its normal skin tissue was taken as control group. The HIF-1α mRNA expression level was detection by real-time PCR. The protein expression of HIF-1α was analyzed by immunohistochemistry. The expression of HIF-1α-related cytokines TGF-β, E-cadherin and VEGF were detected by Western blot. Results Compared with normal tissues(0.29±0.03), the mRNA relative expression of HIF-1α in hypertrophic scar tissue(1.45±0.16)was significantly increased(P<0.05). Immunohistochemistry showed that the positive expression of HIF-1α in hypertrophic scar tissue(70.7%) was significantly higher than that in normal tissues(8.54%,P<0.05). Western blot showed that compared with normal tissues, the expression of HIF-1α, TGF-β and VEGF in hypertrophic scar tissue were significantly increased, whereas the expression level of E-cadherin was significantly decreased(P <0.05). Conclusion HIF-1α was highly expressed in hypertrophic scar tissue and participates in the development of hypertrophic scar by regulating the expression of downstream cytokines TGF-β, VEGF and E-cadherin.
引文
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[15]Hatfield SM,Kjaergaard J,Lukashev D,et al.Systemic oxygenation weakens the hypoxia and hypoxia inducible factor 1α-dependent and extracellular adenosine-mediated tumor protection[J].J Mol Med(Berl),2014,92(12):1283-1292.
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[17]Wulandari E,Jusman SW,Moenadjat Y,et al.Expressions of collagen Iand III in hypoxic keloid tissue[J].Kobe J Med Sci,2016,62(3):e58-e69.
[2]Del Toro D,Dedhia R,Tollefson TT.Advances in scar management:prevention and management of hypertrophic scars and keloids[J].Curr Opin Otolaryngol Head Neck Surg,2016,24(4):322-329.
[3]Ogawa R,Akaishi S,Kuribayashi S,et al.Keloids and hypertrophic scars can now be cured completely:recent progress in our understanding of the pathogenesis of keloids and hypertrophic scars and the most promising current therapeutic strategy[J].J Nippon Med Sch,2016,83(2):46-53.
[4]Halligan DN,Murphy SJ,Taylor CT.The hypoxia-inducible factor(HIF)couples immunity with metabolism[J].Semin Immunol,2016,28(5):469-477.
[5]Kumar V,Gabrilovich DI.Hypoxia-inducible factors in regulation of immune responses in tumour microenvironment[J].Immunology,2014,143(4):512-519.
[6]Makboul M,Makboul R,Abdelhafez AH,et al.Evaluation of the effect of fractional CO2 laser on histopathological picture and TGF-β1 expression in hypertrophic scar[J].J Cosmet Dermatol,2014,13(3):169-179.
[7]Wang X,Gao Z,Wu X,et al.Inhibitory effect of TGF-βpeptide antagonist on the fibrotic phenotype of human hypertrophic scarfibroblasts[J].Pharm Biol,2016,54(7):1189-1197.
[8]Kwak DH,Bae TH,Kim WS,et al.Anti-vascular endothelial growth factor(bevacizumab)therapy reduces hypertrophic scarformation in a rabbit ear wounding model[J].Arch Plast Surg,2016,43(6):491-497.
[9]Lamouille S,Xu J,Derynck R.Molecular mechanisms of epithelialmesenchymal transition[J].Nat Rev Mol Cell Biol,2014,15(3):178-196.
[10]Lee WJ,Park JH,Shin JU,et al.Endothelial-to-mesenchymal transition induced by Wnt 3a in keloid pathogenesis[J].Wound Repair Regen,2015,23(3):435-442.
[11]Nath B,Szabo G.Hypoxia and hypoxia inducible factors:diverse roles in liver diseases[J].Hepatology,2012,55(2):622-633.
[12]Cavadas MAS,Cheong A,Taylor CT.The regulation of transcriptional repression in hypoxia[J].Exp Cell Res,2017,356(2):173-181.
[13]Dengler VL,Galbraith M,Espinosa JM.Transcriptional regulation by Hypoxia inducible factors[J].Crit Rev Biochem Mol Biol,2014,49(1):1-15.
[14]Taylor CT,Colgan SP.Regulation of immunity and inflammation by Hypoxia in immunological niches[J].Nat Rev Immunol,2017,17(12):774-785.
[15]Hatfield SM,Kjaergaard J,Lukashev D,et al.Systemic oxygenation weakens the hypoxia and hypoxia inducible factor 1α-dependent and extracellular adenosine-mediated tumor protection[J].J Mol Med(Berl),2014,92(12):1283-1292.
[16]Barsoum IB,Smallwood CA,Siemens DR,et al.A mechanism of hypoxia-mediated escape from adaptive immunity in cancer cells[J].Cancer Res,2014,74(3):665-674.
[17]Wulandari E,Jusman SW,Moenadjat Y,et al.Expressions of collagen Iand III in hypoxic keloid tissue[J].Kobe J Med Sci,2016,62(3):e58-e69.