PDF(Pubmed)
Abstract：
UNASSIGNED: Integrin-dependent cell adhesion and migration play important roles in systemic sclerosis (SSc). The roles of integrin activating molecules including talins and kindlins, however, are unclear in SSc.
UNASSIGNED: We aimed to explore the function of integrin activating molecules in SSc.
UNASSIGNED: Transcriptome analysis of skin datasets of SSc patients was performed to explore the function of integrin-activating molecules including talin1, talin2, kindlin1, kindlin2 and kindlin3 in SSc. Expression of talin1 in skin tissue was assessed by multiplex immunohistochemistry staining. Levels of talin1 in serum were determined by ELISA. The effects of talin1 inhibition were analyzed in human dermal fibroblasts by real-time PCR, western blot and flow cytometry.
UNASSIGNED: We identified that talin1 appeared to be the primary integrin activating molecule involved in skin fibrosis of SSc. Talin1 was significantly upregulated and positively correlates with the modified Rodnan skin thickness score (mRSS) and the expression of pro-fibrotic biomarkers in the skin lesions of SSc patients. Further analyses revealed that talin1 is predominantly expressed in the dermal fibroblasts of SSc skin and promotes fibroblast activation and collagen production. Additionally, talin1 primarily exerts its effects through integrin β1 and β5 in SSc.
UNASSIGNED: Overexpressed talin1 is participated in skin fibrosis of SSc, and talin1 appears to be a potential new therapeutic target for SSc.
UNASSIGNED: We aimed to explore the function of integrin activating molecules in SSc.
UNASSIGNED: Transcriptome analysis of skin datasets of SSc patients was performed to explore the function of integrin-activating molecules including talin1, talin2, kindlin1, kindlin2 and kindlin3 in SSc. Expression of talin1 in skin tissue was assessed by multiplex immunohistochemistry staining. Levels of talin1 in serum were determined by ELISA. The effects of talin1 inhibition were analyzed in human dermal fibroblasts by real-time PCR, western blot and flow cytometry.
UNASSIGNED: We identified that talin1 appeared to be the primary integrin activating molecule involved in skin fibrosis of SSc. Talin1 was significantly upregulated and positively correlates with the modified Rodnan skin thickness score (mRSS) and the expression of pro-fibrotic biomarkers in the skin lesions of SSc patients. Further analyses revealed that talin1 is predominantly expressed in the dermal fibroblasts of SSc skin and promotes fibroblast activation and collagen production. Additionally, talin1 primarily exerts its effects through integrin β1 and β5 in SSc.
UNASSIGNED: Overexpressed talin1 is participated in skin fibrosis of SSc, and talin1 appears to be a potential new therapeutic target for SSc.
摘要：
■整合素依赖性细胞粘附和迁移在系统性硬化症（SSc）中起重要作用。整合素激活分子包括talins和kindlins的作用，然而,在SSc中不清楚。
■我们旨在探索SSc中整合素激活分子的功能。
■对SSc患者皮肤数据集进行转录组分析，以探索SSc中整合素激活分子包括talin1，talin2，kindlin1，kindlin2和kindlin3的功能。通过多重免疫组织化学染色评估皮肤组织中的talin1表达。ELISA法测定血清中的talin1水平。通过实时PCR在人真皮成纤维细胞中分析了talin1抑制的作用，蛋白质印迹和流式细胞术。
■我们确定，距蛋白1似乎是参与SSc皮肤纤维化的主要整合素激活分子。Talin1显著上调，并与SSc患者皮肤病变中改良的Rodnan皮肤厚度评分（mRSS）和促纤维化生物标志物的表达呈正相关。进一步的分析表明，talin1主要在SSc皮肤的真皮成纤维细胞中表达，并促进成纤维细胞活化和胶原蛋白产生。此外,talin1主要通过SSc中的整合素β1和β5发挥作用。
■过度表达的距骨蛋白1参与了SSc的皮肤纤维化，和talin1似乎是SSc的潜在新治疗靶点。
■我们旨在探索SSc中整合素激活分子的功能。
■对SSc患者皮肤数据集进行转录组分析，以探索SSc中整合素激活分子包括talin1，talin2，kindlin1，kindlin2和kindlin3的功能。通过多重免疫组织化学染色评估皮肤组织中的talin1表达。ELISA法测定血清中的talin1水平。通过实时PCR在人真皮成纤维细胞中分析了talin1抑制的作用，蛋白质印迹和流式细胞术。
■我们确定，距蛋白1似乎是参与SSc皮肤纤维化的主要整合素激活分子。Talin1显著上调，并与SSc患者皮肤病变中改良的Rodnan皮肤厚度评分（mRSS）和促纤维化生物标志物的表达呈正相关。进一步的分析表明，talin1主要在SSc皮肤的真皮成纤维细胞中表达，并促进成纤维细胞活化和胶原蛋白产生。此外,talin1主要通过SSc中的整合素β1和β5发挥作用。
■过度表达的距骨蛋白1参与了SSc的皮肤纤维化，和talin1似乎是SSc的潜在新治疗靶点。
