Localization, function and regulation of the two intestinal fatty acid-binding protein types

Abstract

Although intestinal (I) and liver (L) fatty acid binding proteins (FABP) have been widely studied, the physiological significance of the presence of the two FABP forms (I- and L-FABP) in absorptive cells remains unknown as do the differences related to their distribution along the crypt-villus axis, regional expression, ontogeny and regulation in the human intestine. Our morphological experiments supported the expression of I- and L-FABP as early as 13 weeks of gestation. Whereas cytoplasmic immunofluorescence staining of L-FABP was barely detectable in the lower half of the villus and in the crypt epithelial cells, I-FABP was visualized in epithelial cells of the crypt-villus axis in all intestinal segments until the adult period in which the staining was maximized in the upper part of the villus. Immunoelectron microscopy revealed more intense labeling of L-FABP compared with I-FABP, accompanied with a heterogeneous distribution in the cytoplasm, microvilli and basolateral membranes. By western blot analysis, I- and L-FABP at 15 weeks of gestation appeared predominant in jejunum compared with duodenum, ileum, proximal and distal colon. Exploration of the maturation aspect documented a rise in L-FABP in adult tissues. Permanent transfections of Caco-2 cells with I-FABP cDNA resulted in decreased lipid export, apolipoprotein (apo) biogenesis and chylomicron secretion. Additionally, supplementation of Caco-2 with insulin, hydrocortisone and epidermal growth factor differentially modulated the expression of I- and L-FABP, apo B-48 and microsomal triglyceride transfer protein (MTP), emphasizing that these key proteins do not exhibit a parallel modulation. Overall, our findings indicate that the two FABPs display differences in localization, regulation and developmental pattern.

Intestinal CFTR expression alleviates meconium ileus in cystic fibrosis pigs

“…In line e, we detected CFTR variably present at the apical membrane of crypt epithelial cells. Transgenederived CFTR expression in crypt cells is consistent with the localization of CFTR in wild-type pigs and with the expression pattern of intestinal FABP in human intestine (14,27). Interestingly, in mice transgenic for the rat iFABP promoter driving hCFTR expression, CFTR was localized in both the villous (21) and crypt epithelia (28).…”

Rab11a regulates Syntaxin 3 localization and microvillus assembly in enterocytes

“…All results are representative of three separate experiments. investigations have noted differences in protein expression in enterocytes as they migrate out of the crypt towards the villus (Barnard et al, 1989;Jakab et al, 2011;Levy et al, 2009;Suzuki et al, 2009). We have previously observed in duodenal samples from microvillus inclusion disease patients that the brush borders in enterocytes of the proximal villus are intact (Knowles et al, 2014); loss of microvilli and development of microvillus inclusions only occur in the upper half of the villus.…”

Polycomb repressive complex 2 impedes intestinal cell terminal differentiation

“…The data presented herein on committed cells points out a distinct role for PRC2 activity in cells located outside of the stem cell compartments, restraining their terminal differentiation. It has to be pointed out however that not all terminal differentiation markers have their expression controlled by PRC2 activity as illustrated with intestinal fatty acid binding protein, another wellcharacterized intestinal terminal differentiation marker (Levy et al, 2009).…”