RRC ID 82489
Author Lai S, Higuchi T, Tsuda M, Sugiyama Y, Morisawa K, Taniguchi T, Sakamoto S.
Title NF90-NF45 is essential for β cell compensation under obesity-inducing metabolic stress through suppression of p53 signaling pathway.
Journal Sci Rep
Abstract The Nuclear Factor 90 (NF90)-NF45 complex has been known to regulate the progression of transcription, mRNA stability, translational inhibition, RNA export and microRNA biogenesis. However, the physiological functions of the NF90-NF45 complex remain unclear. We newly discovered that the NF90-NF45 complex was expressed in primary β cells and established cell lines. Therefore, in this study, we focused on the function of the endogenous NF90-NF45 complex in the β cells. To investigate this issue, we generated β-cell-specific NF90-NF45 deficient mice. These mice exhibited hyperglycaemia and lower plasma insulin levels under a high fat diet together with decreased islet mass. To uncover this mechanism, we performed a whole-genome expression microarray of the total RNA prepared from β cell lines treated with siRNAs targeting both NF90 and NF45. In this result, we found an activation of p53 signaling in the NF90-NF45-knockdown cells. This activation was supported by elevation of luciferase activity derived from a reporter plasmid harboring p53 binding sites in the NF90-NF45-knockdown cells. Furthermore, the knockdown of NF90-NF45 resulted in a significant retardation of the β cell line growth rates. Importantly, a dominant negative form of p53 rescues the growth retardation in BTC6 cells depleted of NF90-NF45, suggesting that NF90-NF45 would be positively involved in β cell proliferation through suppression of p53 signal pathway. Taken together, NF90-NF45 is essential for β cell compensation under obesity-inducing metabolic stress via repression of p53 signaling.
Volume 12(1)
Pages 8837
Published 2022-5-25
DOI 10.1038/s41598-022-12600-y
PII 10.1038/s41598-022-12600-y
PMID 35614067
PMC PMC9132887
MeSH Animals Mice Nuclear Factor 45 Protein* / metabolism Nuclear Factor 90 Proteins* / metabolism Obesity / genetics RNA Signal Transduction Stress, Physiological Tumor Suppressor Protein p53* / metabolism
Resource
Mice RBRC09525