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Angiopoietin-like 4 Enhances the Proliferation and Migration of Tendon Fibroblasts
Sarwat Jamil1, Rouhollah Mousavizadeh, Mani Roshan-Moniri
11Department 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.
Purpose:
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.
Methods:
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.
Results:
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.
Conclusion:
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.