Dermatopontin augments angiogenesis and modulates the expression of transforming growth factor beta 1 and integrin alpha 3 beta 1 in endothelial cells.
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.
Biological Materials Laboratory, CSIR-Central Leather Research Institute, Adyar, Chennai, 600020, India.
Venkat Raghavan
VR
Krishnaswamy
Department of Biotechnology and AU-KBC Research Centre, Anna University, Chennai, India.
Uma Maheshwari
UM
Balaguru
Department of Biotechnology and AU-KBC Research Centre, Anna University, Chennai, India.
Suvro
S
Chatterjee
Biological Materials Laboratory, CSIR-Central Leather Research Institute, Adyar, Chennai, 600020, India. Electronic address: purnasaik.clri@gmail.com.
Purna Sai
PS
Korrapati
D000818:Animals; D002460:Cell Line; D002465:Cell Movement; D049109:Cell Proliferation; D002642:Chick Embryo; D011508:Chondroitin Sulfate Proteoglycans / Q000494:pharmacology*; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D016326:Extracellular Matrix Proteins / Q000494:pharmacology*; D006801:Humans; D039201:Integrin alpha3beta1 / Q000235:genetics / Q000378:metabolism*; D018919:Neovascularization, Physiologic; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*
D011508:Chondroitin Sulfate Proteoglycans; C082019:DPT protein, human; D016326:Extracellular Matrix Proteins; D039201:Integrin alpha3beta1; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta
Angiogenesis; Dermatopontin; Endothelial cells; Extracellular matrix; Wound healing