A Preliminary Study On The Effect Of Propranolol On The Expression And Effect Of Jagged1 And Hey1 In HUVECs

Background:infantile hemangioma is a benign tumor which mainly occurs in skin and soft tissue.It is the most common in infancy.The incidence of hemangioma is about 14%and has an increasing trend.The pathogenesis is considered to be related to abnormal endothelial cell proliferation and abnormal regulation of angiogenesis,but the specific molecular mechanism is still not very clear.Studies have found that many signal pathways in human body are involved in the pathogenesis and regression of infantile hemangioma,including VEDF,Notch,Mtor signal pathway and so on.Most children’s tumors can disappear to varying degrees before the age of 7,and complications such as ulcers and affecting development may occur in the course of the disease.after regression,residual skin damage may be caused to bring physical and mental injury to children.At present,it is agreed that infantile hemangioma should be intervened as soon as possible.During the treatment of children with cardiomyopathy with propranolol,foreign scholars accidentally found that propranolol also had a therapeutic effect on hemangioma.Subsequent studies confirmed that propranolol has a good effect on infantile hemangioma with little adverse reactions.Propranolol has become the first choice for the treatment of infantile hemangioma.However,there is still no clear evidence on how propranolol plays a therapeutic role and how it affects the proliferation of vascular endothelial cells and regulates angiogenesis.It was found that Notchl and Notch3 were overexpressed in Notch pathway in proliferative hemangioma,suggesting that Notch pathway-related molecules play an important role in promoting vascular endothelial cell proliferation.Whether propranolol exerts its therapeutic effect by affecting Notch signaling pathway remains to be further studied.Objective:To explore the mechanism of propranolol in the treatment of infantile hemangioma,the biological behavior of human umbilical vein endothelial cells treated with propranolol was observed,and the expression of Notchl,jagged1,Hey1 and D114 was detected before and after propranolol treatment.Methods:Human umbilical vein endothelial cells(HUVECs)cultured in vitro were treated with propranolol at a certain concentration.The proliferation and apoptosis of HUVECs were detected by CCK-8,and the expression of Notchl,Jaggedl,Hey1,D114 genes and proteins were detected by qRT-PCR and Western Blot.Results:In CCK-8 experiment,the proliferation of cells decreased with the increase of propranolol concentration(P<0.05),and the proliferation decreased with the increase of propranolol concentration(P<0.05),and the proliferation decreased with the increase of propranolol concentration(P<0.05).In flow cytometry,propranolol could affect cell growth and promote endothelial cell apoptosis(P<0.05).In qRT-PCR and Western Blot experiments,propranolol could up-regulate the expression of Notch1,Jagged1 and Hey1,and down-regulate the expression of D114(P<0.05).Conclusions:Propranolol can effectively inhibit the proliferation and promote apoptosis of human umbilical vein endothelial cells.Propranolol can up-regulate the expression of Notchl,Jaggedl and Heyl and down-regulate the expression of D114 in human umbilical vein endothelial cells.It can be inferred that the therapeutic effect of propranolol on hemangioma may be related to the increase of Notch signal pathway ligand Jaggedl expression and activation of Notchl pathway to induce downstream target gene Hey1 expression.