Short-chain fatty acids regulate IGF-binding protein secretion by intestinal epithelial cells.
Gastrointestinal epithelial cells secrete insulin-like growth factor (IGF)-binding proteins (IGFBPs), which modulate the actions of IGFs on cell proliferation and differentiation. Short-chain fatty acids are bacterial metabolites from unabsorbed carbohydrate (including fiber). We hypothesized that they may alter the pattern of IGFBPs secreted by epithelial cells as part of a wider phenomenon by which luminal molecules regulate gastrointestinal epithelial cell signaling. The intestinal epithelial cell line, Caco-2, predominantly secretes IGFBP-3; however, butyrate increased the secretion of IGFBP-2 in a dose-dependent and reversible manner. Butyrate decreased the secretion of IGFBP-3. Butyrate altered only the synthesis and not the cell sorting of IGFBPs because 1) the secretion of IGFBPs remained polarized despite changes in their rates of production, and 2) IGFBP secretion corresponded to mRNA accumulation. The ability of short-chain fatty acids or the fungicide trichostatin A to stimulate IGFBP-2 correlated with their actions on histone acetylation. In conclusion, intestinal epithelial cells respond to short-chain fatty acids by altering secretion of IGFBPs.
Developmental Gastroenterology Laboratory, Combined Program in Pediatric Gastroenterology and Nutrition, Massachusetts General Hospital, Harvard Clinical Nutrition Research Center, Charlestown, Massachusetts 02129, USA.
A
A
Nishimura
M
M
Fujimoto
S
S
Oguchi
R D
RD
Fusunyan
R P
RP
MacDermott
I R
IR
Sanderson
D000230:Adenocarcinoma; D002087:Butyrates / Q000494:pharmacology; D020148:Butyric Acid; D002460:Cell Line; D002462:Cell Membrane / Q000502:physiology; D016764:Cell Polarity; D003110:Colonic Neoplasms; D006801:Humans; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000096:biosynthesis; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000096:biosynthesis; D018974:Insulin-Like Growth Factor Binding Protein 4 / Q000096:biosynthesis; D018969:Insulin-Like Growth Factor Binding Proteins / Q000096:biosynthesis* / Q000378:metabolism; D007413:Intestinal Mucosa / Q000502:physiology*; D007700:Kinetics; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D002087:Butyrates; D018971:Insulin-Like Growth Factor Binding Protein 2; D018972:Insulin-Like Growth Factor Binding Protein 3; D018974:Insulin-Like Growth Factor Binding Protein 4; D018969:Insulin-Like Growth Factor Binding Proteins; D012333:RNA, Messenger; D020148:Butyric Acid