| First Author | Lai S | Year | 2022 |
| Journal | Sci Rep | Volume | 12 |
| Issue | 1 | Pages | 8837 |
| PubMed ID | 35614067 | Mgi Jnum | J:344090 |
| Mgi Id | MGI:7283616 | Doi | 10.1038/s41598-022-12600-y |
| Citation | Lai S, et al. (2022) NF90-NF45 is essential for beta cell compensation under obesity-inducing metabolic stress through suppression of p53 signaling pathway. Sci Rep 12(1):8837 |
| abstractText | 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 beta cells and established cell lines. Therefore, in this study, we focused on the function of the endogenous NF90-NF45 complex in the beta cells. To investigate this issue, we generated beta-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 beta 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 beta 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 beta cell proliferation through suppression of p53 signal pathway. Taken together, NF90-NF45 is essential for beta cell compensation under obesity-inducing metabolic stress via repression of p53 signaling. |
