Qki Affects On The Proliferation And Collagen Synthesis Of Rat Cardlac Fibroblasts

Today's world, cardiovascular disease seriously endangering the health andsafety of human life,heart failure is a common expression to end stage ofcardiovascular diseases. In the United States, about 400,000 cases of heart failurepatients with newly issued, a total of about 3 million people suffering from heartfailure, about 20 million deaths each year. Greater than 65-year-old crowd, thecause of heart failure hospitalization among the first. The annual cost of treatingheart failure in more than 10 billion U.S. dollars. Heart failure is considered thekey issues in the new century, known as the "new epidemic of cardiovasculardisease." Myocardial remodeling is an important pathophysiological basis ofheart failure, including myocardial cells remodeling and myocardial remodeling,the most important part of myocardial remodeling is myocardial fibrosis.Therefore, the reversal of myocardial fibrosis and improve the prevention andtreatment of myocardial remodeling in heart failure is important. QKI is a groupof RNA binding protein recently discovered,encoded by the qking gene, its role in regulating myelin formation has been well known. QKI in heart cells also have awide range of expression, recent studies have determined that it has close to 1430presumed target mRNA,and these include the p27,a cellular cyclin-dependentkinase inhibitor. QKI in the heart cells are playing an unknown impact associatedwith the cell cycle and its role on myocardial remodeling should be doubtful. Inthis study rat cardiac fibroblasts as studied with the mature way of angiotensinâ…¡induced fibrosis model.Objective:To investigate if the QKI RNA binding proteins have beenimplicated in the cardiac fibroblast proliferation and collagen synthesis,extensionthe mechanism of cardiac fibrosis, explore a new method to improve theremodeling of heart.Method:Cardiac fibroblasts were prepared from the heart of neonateSprague-Dawley rat by collagenase digestion solution and Differential adhesionmethod. The angiotensinâ…¡induced CF fibrosis model were treated by QKIoverexpress or Interfere,then procure the results by western-blot,RT-PCR andflow cytometry.Result: Angiotensionâ…¡caused a apparent time related decrease of theexpression of QKI,and get the bottom after 24h.The expression of PCNA,Cyclooxygenase-2( COX-2 )and collagen1a/3a in the CF modle with a high orlow expression level of QKI were obtained by western-blot and RT-PCRmethods,the cell circle was procured by flow cytometry.The data supports that theoverexpress of QKI-6 isoform caused a significant decrease of CFproliferation,and interfere QKI caused a reverse result but might cause anotherinstability of CF cell. The expression of QKI in CF affect little on collagensynthesis.The expression of p27 measured by PT-RCR positive correlated withthe expression level of QKI in CF fibrosis model and situation of high expressed QKI,but correlated rarely in the condition of QKI interference.Conclusion: Our results suggest that QKI negatively regulated theproliferation of CF,by regulating p27 through MAPK-ERK signallingpathway,and may affect on the cell stability in outside stimulation.