| First Author | Li R | Year | 2024 |
| Journal | Physiol Rep | Volume | 12 |
| Issue | 17 | Pages | e70021 |
| PubMed ID | 39261977 | Mgi Jnum | J:359015 |
| Mgi Id | MGI:7732525 | Doi | 10.14814/phy2.70021 |
| Citation | Li R, et al. (2024) miR-495 promotes intestinal epithelial cell apoptosis through downregulation of Sphingosine-1-phosphate. Physiol Rep 12(17):e70021 |
| abstractText | Many pathological conditions lead to defects in intestinal epithelial integrity and loss of barrier function; Sphingosine-1-phosphate (S1P) has been shown to augment intestinal barrier integrity, though the exact mechanisms are not completely understood. We have previously shown that overexpression of Sphingosine Kinase 1 (SphK1), the rate limiting enzyme for S1P synthesis, significantly increased S1P production and cell proliferation. Here we show that microRNA 495 (miR-495) upregulation led to decreased levels of SphK1 resultant from a direct effect at the SphK1 mRNA. Increasing expression of miR-495 in intestinal epithelial cells resulted in decreased proliferation and increased susceptibility to apoptosis. Transgenic expression of miR-495 inhibited mucosal growth, as well as decreased proliferation in the crypts. The intestinal villi also expressed decreased levels of barrier proteins and exaggerated damage upon exposure to cecal ligation-puncture. These results implicate miR-495 as a critical negative regulator of intestinal epithelial protection and proliferation through direct regulation of SphK1, the rate limiting enzyme critical for production of S1P. |
