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真皮桥连蛋白增强血管生成,并调节内皮细胞中转化生长因子β 1 和整合素α 3 β 1 的表达。

Dermatopontin augments angiogenesis and modulates the expression of transforming growth factor beta 1 and integrin alpha 3 beta 1 in endothelial cells.

机构信息

Biological Materials Laboratory, CSIR-Central Leather Research Institute, Adyar, Chennai, 600020, India.

Department of Biotechnology and AU-KBC Research Centre, Anna University, Chennai, India.

出版信息

Eur J Cell Biol. 2017 May;96(3):266-275. doi: 10.1016/j.ejcb.2017.02.007. Epub 2017 Mar 11.

Abstract

Dermatopontin (DPT) is a matricellular protein with cardinal roles in cutaneous wound healing. The protein is also reported to be altered in various anomalies including cancer. The present study is aimed to unravel the role of DPT in angiogenesis which is imperative in many physiological and pathological processes. DPT's capabilities on promoting angiogenesis were assessed using various in vitro and ex vivo systems. The results indicated that DPT enhances cell motility and induces lamellipodia formation in endothelial cells. Additionally, we noticed that DPT stimulates tube formation in endothelial cells when plated on a matrigel substrate. However, it was observed that DPT had no effect on the proliferation of endothelial cells even at higher concentrations and prolonged treatment periods. Additional experiments on CAM and aortic arch assays apparently depicted that DPT promotes neovascularisation and tube sprouting, thus unraveling its prominent role in angiogenesis. Further, PCR analysis revealed that endothelial cells are devoid of DPT expression, but when exogenously supplied, modulates the expression of transforming growth factor β1 and integrin α3β1 which are reported to have crucial roles in endothelial cell behaviour during angiogenesis. In conclusion, DPT possess vital pro-angiogenic properties and thus retains promising therapeutic values in managing chronic wounds and cancer.

摘要

真皮桥蛋白(DPT)是一种基质细胞蛋白,在皮肤伤口愈合中具有重要作用。该蛋白也被报道在包括癌症在内的各种异常中发生改变。本研究旨在揭示 DPT 在血管生成中的作用,血管生成在许多生理和病理过程中都是必不可少的。使用各种体外和体内系统评估了 DPT 促进血管生成的能力。结果表明,DPT 增强了内皮细胞的细胞迁移能力,并诱导了伪足的形成。此外,我们注意到,当在基质胶基底上培养时,DPT 刺激内皮细胞的管状形成。然而,即使在较高浓度和延长的处理时间下,DPT 对内皮细胞的增殖也没有影响。CAM 和主动脉弓测定的额外实验明显表明,DPT 促进血管新生和管突形成,从而揭示了其在血管生成中的重要作用。此外,PCR 分析显示内皮细胞缺乏 DPT 表达,但当外源性供应时,调节转化生长因子β1 和整合素α3β1 的表达,这两种因子被报道在血管生成过程中对内皮细胞行为具有重要作用。总之,DPT 具有重要的促血管生成特性,因此在治疗慢性伤口和癌症方面具有有前途的治疗价值。

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