title: Differentiation-dependent regulation of intestinal vitamin B(2) uptake: studies utilizing human-derived intestinal epithelial Caco-2 cells and native rat intestine.
abstract: Intestinal epithelial cells undergo differentiation as they move from the crypt to the villi, a process that is associated with up- and downregulation in expression of a variety of genes, including those involved in nutrient absorption. Whether the intestinal uptake process of vitamin B(2) [riboflavin (RF)] also undergoes differentiation-dependent regulation and the mechanism through which this occurs are not known. We used human-derived intestinal epithelial Caco-2 cells and native rat intestine as models to address these issues. Caco-2 cells showed a significantly higher carrier-mediated RF uptake in post- than preconfluent cells. This upregulation was associated with a significantly higher level of protein and mRNA expression of the RF transporters hRFVT-1 and hRFVT-3 in the post- than preconfluent cells; it was also accompanied with a significantly higher rate of transcription of the respective genes (SLC52A1 and SLC52A3), as indicated by the higher level of expression of heterogeneous nuclear RNA and higher promoter activity in post- than preconfluent cells. Studies with native rat intestine also showed a significantly higher RF uptake by epithelial cells of the villus tip than epithelial cells of the crypt; this again was accompanied by a significantly higher level of expression of the rat RFVT-1 and RFVT-3 at the protein, mRNA, and heterogeneous nuclear RNA levels. These findings show, for the first time, that the intestinal RF uptake process undergoes differentiation-dependent upregulation and suggest that this is mediated (at least in part) via transcriptional mechanisms.
authors: Department of Medicine, University of California, Irvine, CA, USA.
authors: Veedamali S
authors: VS
authors: Subramanian
authors: Abhisek
authors: A
authors: Ghosal
authors: Sandeep B
authors: SB
authors: Subramanya
authors: Christian
authors: C
authors: Lytle
authors: Hamid M
authors: HM
authors: Said
mesh_terms: D000818:Animals; D018938:Caco-2 Cells; D002454:Cell Differentiation / Q000502:physiology; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D007408:Intestinal Absorption / Q000502:physiology*; D007413:Intestinal Mucosa / Q000166:cytology / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D012256:Riboflavin / Q000493:pharmacokinetics*; D014158:Transcription, Genetic / Q000502:physiology; D014803:Vitamin B Complex / Q000493:pharmacokinetics
chemical_list: D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; C486729:RFT1 protein, human; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; C548553:SLC52A3 protein, human; C581655:SLC52A3 protein, rat; D014803:Vitamin B Complex; D012256:Riboflavin