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

• Published in: European journal of cell biology Vol. 96; no. 3; pp. 266 - 275
• Main Authors: Krishnaswamy, Venkat Raghavan, Balaguru, Uma Maheshwari, Chatterjee, Suvro, Korrapati, Purna Sai
• Format: Journal Article
• Language: English
• Published: Germany Elsevier GmbH 01.05.2017
• Subjects: Angiogenesis; Animals; Cell Line; Cell Movement; Cell Proliferation; Chick Embryo; Chondroitin Sulfate Proteoglycans - pharmacology; Dermatopontin; Endothelial cells; Endothelial Cells - drug effects; Endothelial Cells - metabolism; Endothelial Cells - physiology; Endothelium, Vascular - cytology; Endothelium, Vascular - drug effects; Endothelium, Vascular - physiology; Extracellular matrix; Extracellular Matrix Proteins - pharmacology; Humans; Integrin alpha3beta1 - genetics; Integrin alpha3beta1 - metabolism; Neovascularization, Physiologic; Recombinant Proteins; Transforming Growth Factor beta - genetics; Transforming Growth Factor beta - metabolism; Wound healing; Angiogenesis; Extracellular matrix; Dermatopontin; Wound healing; Endothelial cells
• ISSN: 0171-9335; 1618-1298
• DOI: 10.1016/j.ejcb.2017.02.007

•Dermatopontin (DPT) is a matrix protein with key functions during wound healing.•DPT’s levels are altered in several pathologies where an unwarranted vasculature is witnessed, yet its role in angiogenesis is undetermined.•Here, we showed that DPT promotes angiogenesis significantly and thus, holds promising potential in managing cancer and tissue repair. 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.