Hypoxia-inducible factor-1α-mediated SERPINE-1 expression in ischemic urinary bladder

초록

BackgroundIncreasing cyclic pressure on the bladder in urodynamic changes results in tissue hypertrophy, triggering hypoxia-related molecular mechanisms, and promoting bladder tissue remodeling. The etiology and causative mechanisms of Hif-1 alpha-derived tissue remodeling remain unclear.ObjectiveThis study aimed to examine the hypothesis that hypoxia-related pathways and potent gene expression profiles may be associated with pathological symptoms such as detrusor over-activity and increased urinary frequency. Thus, we suggest that Hif-1 alpha-mediated target gene expression is related to the major connections between urodynamic changes and differentially expressed genes (DEGs) in one control (Sham) and two experimental models, partial bladder outlet obstruction (PBOO), and de-obstructed (DeObs) rats.ResultsIn cystometric measurements, the pressure and volume of the PBOO and DeObs rat groups showed significant differences compared to the sham group, but there were no significant differences between the PBOO and DeObs groups. Among the DEGs, the expression levels of many genes largely altered in the PBOO group were normalized in the DeObs group. These differences between the activities of cystometric parameters and RNA-seq-based DEGs patterns, identified in the comparisons of the three groups, were not consistent. In contrast, the five genes (ALDH3A1, CYP1A1, SERPINE1, CYBB, and PLOD2), based on the FPKM units, were the most predictable, and Hif-1 alpha-induced SERPINE1 and PLOD2 genes might be related to the progression of bladder tissue remodeling, such as hypertrophy and fibrosis. SERPINE1 dominantly expressed in BSMCs was one gene matched between protein expression levels and enriched FPKM values.ConclusionsExpression of Hif-1 alpha-mediated SERPINE1 induced under hypoxia may be linked to pathological bladder tissue remodeling outcomes. Thus, we propose that alterations in SERPINE1 expression induced in cyclic hypoxia-exposed bladders may be related to tissue hypertrophy and/or fibrosis.

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