IGFBP1 stabilizes Umod expression through m6A modification to inhibit the occurrence and development of cystitis by blocking NF-κB and ERK signaling pathways.

Autor: Yuan Z; Department of Infectious Disease, Nanjing First Hospital, Nanjing Medical University, Nanjing 210000, PR China., Wang W; Department of Infectious Disease, Nanjing First Hospital, Nanjing Medical University, Nanjing 210000, PR China., Song S; Department of Infectious Disease, Nanjing First Hospital, Nanjing Medical University, Nanjing 210000, PR China., Ling Y; Department of Infectious Disease, Nanjing First Hospital, Nanjing Medical University, Nanjing 210000, PR China., Xu J; Department of Neurology, Nanjing First Hospital, Nanjing Medical University, Nanjing 210000, PR China. Electronic address: xujing850408@163.com., Tao Z; Department of Infectious Disease, Nanjing First Hospital, Nanjing Medical University, Nanjing 210000, PR China. Electronic address: tz1010@126.com.
Jazyk: angličtina
Zdroj: International immunopharmacology [Int Immunopharmacol] 2024 Jun 15; Vol. 134, pp. 111997. Date of Electronic Publication: 2024 May 17.
DOI: 10.1016/j.intimp.2024.111997
Abstrakt: 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.
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Databáze: MEDLINE
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