The Mechanism Research Of Nulp1 In Hypertrophic Cardiomyopathy

Beisic Helix-Loop-Helix(BHLH)protein is a special kind of transcription factors in eukaryotes,playing an important role in regulating nerve,muscle cells,cancer,heart and blood cells occur in the process.nulp1 gene is a human heart development candidate genes,also is a kind transcription factors of BHLH.Studies have showed that the BHLH proteins play an important regulatory role on the occurrence and development of a variety of organizations in the heart suggesting that nulp1 may be an important regulatory factor,and nulp1 gene may be associated with cardiac development and function.nulp1 is a new heart development candidate gene in our laboratory.There are 18 exons,the 2031 bp of ORF,encoding a protein of 676 amino acid residues in the gene.Compared to normal mice,nulp1 gene expression in ISO stimulated hypertrophy cardiac is lower.And we analysis phenotypic of genetically modified mice.Through the injection of ISO for 7 days,induce cardiac hypertrophy in nulp1 transgene mice.RT-PCR analysis related hypertrophy gene expression,ANF,?-MHC,SKA is lower in nulp1 transgene mice after the pathological stimulation.And through nulp1 gene RNAi virus infection with the newborn rat myocardial cells,it was found that ANF,?-MHC,SKA increases more significantly under the PE induction.The above experiments indicatenulp1 as a negative regulatory factor might play a role of myocardial hypertrophy,and nulp1 may inhibit cardiac hypertrophy.Our laboratory has previously obtained the protein of FHL2 from the adult heart library,as a candidate of interacting with nulp1.The protein of FHL2 specially expresses in the heart tissue.The previously result has demonstrated that two proteins have interaction with each other in the HEK293 cells and in adult mice,which suggests the interaction between nulp1 and FHL2 may mediate cardiac hypertrophy occurred.nulp1 and FHL2 together made the ?-Catenin protein degradation suggesting that nulp1 may take part in the Wnt/?-Catenin signaling pathway.But its specific mechanism remains to be studied.