Jamil Sarwat, Mousavizadeh Rouhollah, Roshan-Moniri Mani, Tebbutt Scott J, McCormack Robert G, Duronio Vincent, Scott Alex
1Department of Physical Therapy, Centre for Hip Health and Mobility, Vancouver Coastal Health Research Institute, University of British Columbia, Vancouver, BC, CANADA; 2Department of Medicine, Jack Bell Research Centre, University of British Columbia, Vancouver, BC, CANADA; 3Department of Urologic Sciences, Vancouver Prostate Centre, University of British Columbia, Vancouver, BC, CANADA; 4Division of Respiratory Medicine, Department of Medicine, University of British Columbia, Vancouver, BC, CANADA; 5Prevention of Organ Failure (PROOF) Centre of Excellence, Vancouver, CANADA; and 6Department of Orthopaedic Surgery, University of British Columbia, Vancouver, CANADA.
Med Sci Sports Exerc. 2017 Sep;49(9):1769-1777. doi: 10.1249/MSS.0000000000001294.
Angiopoietin-like 4 (ANGPTL4) is known to play a variety of roles in the response to exercise, and more recently has been shown to enhance the healing of tendon, a fibrous load-bearing tissue required for efficient movement. The objective of the current study was to further explore the mechanisms of ANGPTL4's effect on tendon cells using a gene array approach.
Human tendon fibroblasts were treated with recANGPTL4 and their global transcriptome response analyzed after 4 and 24 h. We also conducted functional studies using tendon fibroblasts derived from human subjects, cultured in the presence or absence of applied cyclic stretch and/or siRNA for ANGPTL4, and as confirmation we also used tendon cells from wild type (ANGPTL4 +/+) or knockout (ANGPTL4-/-) mice.
The leading functions of ANGPTL4 predicted by the resulting pathway analysis were cell movement and proliferation. The experiments demonstrated that ANGPTL4 significantly enhanced tendon cell proliferation and the cell cycle progression, as well as adhesion and migration.
Taken together, these findings provide novel molecular insights into the effect of ANGPTL4, a multifunctional protein that regulates the physiological response to exercise, on fundamental tendon cell functions.
已知血管生成素样4（ANGPTL4）在运动反应中发挥多种作用，最近还显示其能促进肌腱愈合，肌腱是高效运动所需的纤维承重组织。本研究的目的是使用基因阵列方法进一步探索ANGPTL4对肌腱细胞作用的机制。
用重组ANGPTL4处理人肌腱成纤维细胞，并在4小时和24小时后分析其整体转录组反应。我们还使用来自人类受试者的肌腱成纤维细胞进行功能研究，在有或没有施加循环拉伸和/或针对ANGPTL4的小干扰RNA（siRNA）的情况下进行培养，并且作为验证，我们还使用了野生型（ANGPTL4 +/+）或基因敲除（ANGPTL4-/-）小鼠的肌腱细胞。
通过所得通路分析预测，ANGPTL4的主要功能是细胞运动和增殖。实验表明，ANGPTL4显著增强了肌腱细胞增殖、细胞周期进程以及黏附和迁移。
综上所述，这些发现为ANGPTL4这一调节运动生理反应的多功能蛋白对肌腱细胞基本功能的影响提供了新的分子见解。
