Reference - Detail
| 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 |
| IF | 3.998 |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | X(Twitter) |
| Total number of mentions | 1 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Mice | RBRC09525 |