| First Author | Kim YK | Year | 2025 |
| Journal | Biochim Biophys Acta Mol Cell Biol Lipids | Volume | 1870 |
| Issue | 2 | Pages | 159584 |
| PubMed ID | 39645027 | Mgi Jnum | J:359860 |
| Mgi Id | MGI:7789966 | Doi | 10.1016/j.bbalip.2024.159584 |
| Citation | Kim YK, et al. (2024) The intestine-specific homeobox (ISX) modulates beta-carotene-dependent regulation of microsomal triglyceride transfer protein (MTP) in a tissue-specific manner. Biochim Biophys Acta Mol Cell Biol Lipids 1870(2):159584 |
| abstractText | Vitamin A is an essential nutrient crucial to ensuring proper mammalian embryonic development. beta-Carotene is the most prevalent form of vitamin A in food that, when transferred in its intact form from mother to the developing tissues, can serve as an in situ source of retinoic acid, the active form of vitamin A. We have previously provided evidence that the maternal-fetal transfer of beta-carotene across the placenta is mediated by lipoproteins and that beta-carotene itself regulates placenta lipoprotein biogenesis by means of its derivatives beta-apo-10'-carotenoids and retinoic acid. These metabolites exert antagonistic transcriptional activity on placental microsomal triglyceride transfer protein (MTP) and apolipoprotein B (APOB), two key players of lipoprotein biosynthesis. Here, we analyzed the time-dependency of this regulation over the course of 24 h upon a single maternal administration of beta-carotene. We also tested the hypothesis that the transcriptional repressor intestine-specific homeobox (ISX) plays a role in the regulation of Mttp in placenta. We observed that ISX is expressed in placenta of mouse dams and is regulated by beta-carotene availability. Furthermore, we demonstrated that the absence of Isx disrupts the beta-carotene-mediated regulation of placental MTP. We also showed that this mechanism is organ-specific, as it was not observed in enterocytes of the intestine, a major place of Isx expression. Therefore, we identified ISX as a "master" regulator of a placental beta-carotene-dependent transcriptional regulatory cascade that fine-tunes the flux of provitamin A carotenoid towards the developing fetus. |
