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跨膜蛋白45A对瘢痕疙瘩成纤维细胞合成细胞外基质的影响

Effect of transmembrane protein 45A on extracellular matrix synthesis by keloid-derived fibroblasts
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摘要 目的研究跨膜蛋白45A(TMEM45A)在瘢痕疙瘩组织及成纤维细胞中的表达,探讨其对瘢痕疙瘩成纤维细胞(KF)细胞外基质(ECM)的影响。方法收集2019年1月至2020年12月期间在延边大学附属医院皮肤科及泌尿外科手术切除的瘢痕疙瘩和正常包皮组织标本,采用Western印迹法检测瘢痕疙瘩组织及KF中TMEM45A蛋白表达情况。将KF分成两组,分别通过特异性TMEM45A小干扰RNA(siRNA)和对照siRNA转染,进而采用Western印迹法检测TMEM45A基因的下调对肌成纤维细胞标志性蛋白(α平滑肌肌动蛋白)及ECM相关蛋白表达的影响。结果与正常皮肤组织(1.00±0.11)及成纤维细胞(1.00±0.20)相比,TMEM45A在瘢痕疙瘩(0.26±0.05)及KF(0.41±0.09)中的表达显著降低(t值分别为10.76、4.75,P值分别<0.001,=0.009)。TMEM45A特异性siRNA组中α-平滑肌肌动蛋白(t=-5.98,P=0.004)及ECM蛋白Ⅰ型、Ⅲ型胶原蛋白(t值分别为-4.57、-4.90,P值分别为0.010、0.008)和纤连蛋白(t=-7.19,P=0.002)的表达均高于对照siRNA组。结论瘢痕疙瘩中低表达的TMEM45A可能通过促进ECM生成在瘢痕疙瘩发病过程中起重要作用。 Objective To determine the expression of transmembrane protein 45A(TMEM45A)in keloid tissues and fibroblasts,and to evaluate its effect on extracellular matrix(ECM)synthesis by keloid-derived fibroblasts(KFs).Methods Samples of surgically excised keloid and normal foreskin tissues were collected from the Department of Dermatology and Department of Urology of Yanbian University Hospital from January 2019 to December 2020,and TMEM45A protein expression was determined in keloid tissues and KFs by Western blot analysis.KFs were divided into TMEM45A-specific small interfering RNA(siRNA)group and control siRNA group to be transfected with the TMEM45A-specific siRNA and control siRNA respectively.Then,Western blot analysis was performed to evaluate the effects of down-regulation of the TMEM45A gene on the expression of myofibroblast marker protein(α-smooth muscle actin)and ECM-related proteins.Results Compared with normal skin tissues(1.00±0.11)and fibroblasts(1.00±0.20),TMEM45A expression levels significantly decreased in keloid tissues(0.26±0.05)and KFs(0.41±0.09),respectively(t=10.76,4.75,P<0.001,=0.009,respectively).The expression levels ofα-smooth muscle actin,ECM-related typeⅠcollagen,typeⅢcollagen,and fibronectin were significantly higher in the TMEM45A-specific siRNA group than in the control siRNA group(t=-5.98,-4.57,-4.90,-7.19,P=0.004,0.010,0.008,0.002,respectively).Conclusion Lowly expressed TMEM45A in keloids may play an important role in the pathogenesis of keloids by promoting ECM synthesis.
作者 刘晨阳 元星花 支嘉慧 库玛丽 卢博 徐玮璐 金哲虎 Liu Chenyang;Yuan Xinghua;Zhi Jiahui;Hem Kumari Rai;Lu Bo;Xu Weilu;Jin Zhehu(Department of Dermatology,Yanbian University Hospital,Yanji 133000,Jilin,China)
出处 《中华皮肤科杂志》 CAS CSCD 北大核心 2023年第7期666-669,共4页 Chinese Journal of Dermatology
基金 国家自然科学基金(81960561、81903196)。
关键词 跨膜蛋白45A 瘢痕疙瘩 成纤维细胞 细胞外基质 Transmembrane protein 45A Keloid Fibroblasts Extracellular matrix
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