ABSTRACT
Cystitis is a common disease closely associated with urinary tract infections, and the specific mechanisms underlying its occurrence and development remain largely unknown. In this study, we discovered that IGFBP1 suppresses the occurrence and development of cystitis by stabilizing the expression of Umod through m6A modification, inhibiting the NF-κB and ERK signaling pathways. Initially, we obtained a bladder cystitis-related transcriptome dataset from the GEO database and identified the characteristic genes Umod and IGFBP1. Further exploration revealed that IGFBP1 in primary cells of cystitis can stabilize the expression of Umod through m6A modification. Overexpression of both IGFBP1 and Umod significantly inhibited cell apoptosis and the NF-κB and ERK signaling pathways, ultimately suppressing the production of pro-inflammatory factors. Finally, using a rat model of cystitis, we demonstrated that overexpression of IGFBP1 stabilizes the expression of Umod, inhibits the NF-κB and ERK signaling pathways, reduces the production of pro-inflammatory factors, and thus prevents the occurrence and development of cystitis. Our study elucidates the crucial role of IGFBP1 and Umod in cystitis and reveals the molecular mechanisms that inhibit the occurrence and development of cystitis. This research holds promise for offering new insights into the treatment of cystitis in the future.
Subject(s)
Cystitis , Insulin-Like Growth Factor Binding Protein 1 , MAP Kinase Signaling System , NF-kappa B , Rats, Sprague-Dawley , Animals , Female , Humans , Rats , Apoptosis , Cystitis/metabolism , Disease Models, Animal , Insulin-Like Growth Factor Binding Protein 1/metabolism , Insulin-Like Growth Factor Binding Protein 1/genetics , NF-kappa B/metabolism , Urinary Bladder/pathology , Urinary Bladder/metabolismABSTRACT
Nonalcoholic fatty liver disease (NAFLD) is the most common fatty liver disease in developed countries, in which fat accumulation in the liver is induced by nonalcoholic factors. The present study was conducted to identify NAFLDassociated long noncoding RNAs (lncRNAs), mRNAs and microRNAs (miRNAs). The microarray dataset GSE72756, which included 5 NAFLD liver tissues and 5 controls, was acquired from the Gene Expression Omnibus database. Differentially expressed lncRNAs (DElncRNAs) and mRNAs (DEmRNAs) were detected using the pheatmap package. Using the clusterProfiler package and Cytoscape software, enrichment and proteinprotein interaction (PPI) network analyses were conducted to evaluate the DEmRNAs. Next, the miRNAlncRNAmRNA interaction network was visualized using Cytoscape software. Additionally, RP11279F6.1 and AC004540.4 expression levels were analyzed by reverse transcription quantitative polymerase chain reaction. There were 318 DElncRNAs and 609 DEmRNAs identified in the NAFLD tissues compared with the normal tissues. Jun protooncogene, AP1 transcription factor subunit (JUN), which is regulated by AC004540.4 and RP11279F6.1, exhibited higher degree compared with other nodes in the PPI network. Furthermore, miR4093p and miR139 (targeting JUN) were predicted as PPI network nodes. In the miRNAlncRNAmRNA network, miR20a and Bcell lymphoma 2like 11 (BCL2L11) were among the top 10 nodes. Additionally, BCL2L11, AC004540.4 and RP11279F6.1 were targeted by miR20a, miR4093p and miR139 in the miRNAlncRNAmRNA network, respectively. RP11279F6.1 and AC004540.4 expression was markedly enhanced in NAFLD liver tissues. These key RNAs may be involved in the pathogenic mechanisms of NAFLD.
