| Cardiac troponin I?cTnI?,a troponin complex subunit on the sarcomere filaments,plays a crucial role in cardiac contraction.It has been reported that different mutations of the cTnI can produce hereditary cardiomyopathy of varying degrees,and it is also a highly specific indicator of peripheral blood in patients with myocardial injury such as acute coronary syndrome.Since the important role of cTnI,it is particularly important to further study its function,especially in the early development of the heart,and explore its specific molecular mechanisms.tnni1b serves as the specific tnni isoform in zebrafish heart without the developmental switch from stnni to ctnni in mammals,and zebrafish have unique advantages in functional research in early cardiac development.In this study,the tnni1b-/-mutant embryos showed pericardial edema,abnormal atrioventricular tube,weakened cardiac contraction and almost no blood flow at 2 dpf and the expression of the specific genes bmp4,cspg2,tbx2b,has2,notch1b and spp1 which characterize the development of the endocardial cushion were also abnormal.Moreover,tnni1b knockout in zebrafish and tnni3 knockdown in H9C2 cells significantly inhibited the ERBB-ERK signaling pathway.By specifically reactivating the ERBB-ERK signaling pathway in the myocardium,it further demonstrated that the abnormal development of atrioventricular valve was the result of inhibition of the ERBB-ERK signaling pathway.In brief,this study found that the ERBB-ERK signaling is involved in the abnormal development of atrioventricular valve in the tnni1b-/-mutant embryos,and the molecular mechanism does not depend on environmental factors such as cardiac contraction and blood flow.This study is an important supplement to the pathogenesis research of cardiac troponin I gene mutation,and provides an important theoretical basis and reference value for the diagnosis and targeted treatment for congenital heart disease,especially the disease with impaired valve development. |
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