The Function Of RNA Binding Protein QKI In Angiotensin Ⅱ Induced Cardiac Hypertrophy

Cardiac hypertrophy refers to the increasing heart volume and thickeningmyocardial fibers at the cellular level. There is almost no change of myocytenumber in cardiac hypertrophy. It is usually an adaptive response of the heart tothe increase pressure. Multiple cardiac physiological and pathological stimuli,such as the growth development, physical challenges, as well as injury, couldincrease the pressure load. It is well established that pathological cardiachypertrophy leads to congestive heart failure, and eventually cardiovascularmortality. Cardiac hypertrophy can also prolong the action potential of myocytes,leading to the arrhythmia and sudden cardiogenic death. So it is of greatsignificance to reveal the underlying mechanism how cardiac hypertrophyoccurs.The occurrence of cardiac hypertrophy includes three sequential steps in amolecular perspective. First, exogenous stimulatory signals of cardiachypertrophy interacts with the cell membrane; second, intracellular signal transduction; third, transcriptional activation of hypertrophy related genes inthe nucleus. It has been a hot topic to explore the molecular mechanism howcardiac hypertrophy occurs, which is also of clinical the cardiovascular basicresearch about how to prevent cardiovascular vicious incident.RNA binding protein QKI is a kind of signal transduction and activation ofRNA(STAR) protein, and there is a single hnRNP K-homology(KH)RNA-binding domain in the protein. The three isoforms (QKI5, QKI6, andQKI7, different at the C-terminal) are derived from the same qkI gene byextensive alternative splicing. RNA binding protein QKI is abundantlyexpressed in nervous system and cardiovascular system. Previous studiesconfirmed that QKI protein has an important role in nervous systemdevelopment, and the deficiency of QKI can result in hypomyelination.However, the functions of QKI protein in cardiovascular system are still largelyunkown. Our study here focus on the expression of RNA binding protein QKIand its role in AngII induced cardiac hypertrophy. The main results are asfollows.1. AngⅡ increased the expression of QKI in cardiac myoblast H9C2cellHypertrophy model was established by stimuli of AngⅡ to cardiacmyoblast H9C2cell. ANP and BNP were tested by quantitative real-time PCR(qRT-PCR), both of which are the markers of cardiac hypertrophy. RT-PCRand western-blotting, as well as indirect immunofluorescence indicated thatthe expression of QKI5and QKI6in hypertrophic cardiomyocytes wereincreased, especially of QKI6.2. The expression of ANP and BNP were increased by knocking downQKI expression Small interfering RNA can inhibits the expression of QKI. The expressionof ANP and BNP were significantly increased which were tested by qRT-PCR.These results suggested QKI could inhibit cardiac hypertrophy.3. The expression of ANP and BNP were decreased by overexpressionof QKIIn order to understand the role of RNA binding protein QKI in cardiachypertrophy, QKI5and QKI6were overexpressed by adnoviruses.Overexpressing QKI6could significantly inhibit the elevation of ANP and BNPinduced by AngII. However, QKI5did not show similar changes.In summary, the above observations provide the first evidence that RNAbinding protein QKI6can inhibit the elevation of ANP and BNP induced byAngII, which hints QKI6can inhibit cardiac hypertrophy, and that provide newideas for the treatment of cardiac hypertrophy.