Cell-Derived Exosomes Ameliorate Erectile Dysfunction In A Rat Model Of Type 2 Diabetes

Background: Diabetic erectile dysfunction(DED)is one of common complications in men with diabetes,which deeply affects patients’ quality of life,and the effects of current therapy are not satisfactory.Currently,many scholars proposed that patients can be benefited of using the stem cell.many studies have shown that stem cells exert their functional benefits through their secretory function.exosomes are one of secretions from stem cell,which play a secretion function.Owing to its bioactive molecules and stability,exosomes have strong potential for disease treatment.During the process of treatment in DED,Exosomes derived from different stem cells hold good promise in rats with DED.In the present project,Meta-analysis was used to conduct systematic review of the therapy of Exosomes derived from Stem Cells to diabetic erectile dysfunction.Using bioinformatic methods,we performed an initial exploration of the molecular mechanism of the theraputic effects of Exosomes derived from stem Cells.Method: Part I :Pubmed、Scopus、web of science、CNKI、VIP、Wanfang were systematic searched from inception to march 2023,subject words and free words include: exosome、extracellular vesicle、nanovesicle、diabetic erectile dysfunction.Two investigators screened the literature and extracted data independently according to the inclusion and exclusion criteria.All analyses were conducted using Rev Man5.3software to assess the relative efficacy of therapies.Part II: Gene expression profiles of DED were extracted from GEO database.Relative software was used to analysis the Differential gene expression in group GSE2457 datasets,which includes 5 experimental samples and 5 control samples.the corresponding target genes of exosome mi RNAs were predicted using the web-based mi RNA-target gene prediction tool,then we analyze the correlation of the differential genes and predicting target genes.Finally,functional enrichment was analyzed by us to confirm related physiological processes,tissue-specificity and signaling pathway.Results: Part I: 7 original articles involving a total of 96 rats were included;among these,48 cases were in the experimental group and 48 cases in the control group.Exosomes derived from stem cells can improve ICP and increase the content of e NOS;n NOS and smooth muscle.Part II: In group GSE2457 datasets,A total of 93 overlapping DEGs were screened,including 42 up-regulated genes and 75 downregulated genes.The mi RNA of exosomes derived from stem cells were identified through database and reference searching,which is inclued:let7a5p、let7b5p、let7f5p、let7g5p、let7i5p、mir10a5p、mir10b5p、mir215p、mir26a5p、mir27a3p、mir30a5p、mir30d5p、mir99a5p、mir148a3p、mir151a3p.After target-genes predicting,we have found 2083 genes.Then we analyzed the correlation of the differential genes and predicting target genes,and 10 genes were ended up with,which include:B4GALT1、COL1A2、CPEB1、FGF5、GPCPD1、GREM1、LPL、NPR3、PDK4、TFRC.After the enrichment analysis,we found that these genes are related to blood vessel development,circulatory system process and cellular response to organonitrogen compound.Tissue-specificity is in smooth muscle and the signaling pathway is main include NF-κB signaling pathway.Conclusion: Exosomes derived from cells can improve ICP and increase the content of e NOS;n NOS and smooth muscle.Exosomes derived from stem cells can improve ICP and increase the content of e NOS;n NOS and smooth muscle.The mechanism may be that the exosome imported mi RNA into cells to play a role in treatment,which is related to B4GALT1、COL1A2、CPEB1、FGF5、GPCPD1、GREM1、LPL、NPR3、PDK4、TFRC.