The Functional Exploration Of MeCP2 In Pancreatic ? Cells And The Positive Effect Of IMPX977 On MeCP2 Target Genes

Islet ? cells are the major component of islets and account for 60%-80%of islet cells.Insulin secreted by pancreatic ? cells is the only hormone that lowers blood glucose.At the same time,it also plays a key role in metabolic regulation.The dysfunction of pancreatic ?-cells is the main cause of type 1 and type 2 diabetes.At present,the number of people affected by type 2 diabetes is as high as 285 million,and that have an increasingly trend.Therefore,the research on the mechanism of islet ? cell dysfunction has attracted increasingly researchers' attention.MeCP2 is a transcription factor widely existing in the body,not only can be combined with methylated DNA involved in the regulation of biological functions,but also can be associated with the corresponding protein and RNA.In the glucose stimulated assay,we found that the expression of MeCP2 increased after glucose stimulated,and the expression of MeCP2 was decreased in the pancreas of type 2 diabetes induced by STZ.This suggests that MeCP2 may be involved in insulin expression or secretion.To further study the role of MeCP2 in insulin expression or secretion,IP-MS,CHIP,RT-PCR,CRISPR/Cas9 and other methods were applied to investigate the role of MeCP2 in pancreatic islet ? cells.It was first found that MeCP2 is involved in islet(3 cellular biological processes with cell proliferation and cell cycle.In addition,we analyzed the possibility of IMPX977(a single component from Malvaceae plants)as a candidate drug to cure Rett syndrome.It is a single-gene disease caused by a mutation in the Mecp2 gene,and that mainly affects girls.No proper medicines or the therapeutic approaches are available in clinic.At present,the screening of drugs targeted Rett syndrome mainly focuses on restoring expression and function of MeCP2 and the downstream target genes of MeCP2.Our previous study found that IMPX977 can evalauated the expression of MeCP2 in the the rat cortex.Therefore,RNA-seq and qPCR were conducted to investigate the impact of IMPX977 on MeCP2 target genes and its mechanism in the transcription level.We first reported that low doses of IMPX977 have a positive effect on the MeCP2 target genes,which laid the theoretical basis for IMPX977 serve as a candidate drug to cure RTT.