title: Dietary fiber enhances TGF-β signaling and growth inhibition in the gut.
abstract: Dietary fiber intake links to decreased risk of colorectal cancers. The underlying mechanisms remain unclear. Recently, we found that butyrate, a short-chain fatty acid produced in gut by bacterial fermentation of dietary fiber, enhances TGF-β signaling in rat intestinal epithelial cells (RIE-1). Furthermore, TGF-β represses inhibitors of differentiation (Ids), leading to apoptosis. We hypothesized that dietary fiber enhances TGF-β's growth inhibitory effects on gut epithelium via inhibition of Id2. In this study, Balb/c and DBA/2N mice were fed with a regular rodent chow or supplemented with a dietary fiber (20% pectin) and Smad3 level in gut epithelium was measured. In vitro, RIE-1 cells were treated with butyrate and TGF-β(1), and cell functions were evaluated. Furthermore, the role of Ids in butyrate- and TGF-β-induced growth inhibition was investigated. We found that pectin feeding increased Smad3 protein levels in the jejunum (1.47 ± 0.26-fold, P = 0.045, in Balb/c mice; 1.49 ± 0.19-fold, P = 0.016, in DBA/2N mice), and phospho-Smad3 levels (1.92 ± 0.27-fold, P = 0.009, in Balb/c mice; 1.83 ± 0.28-fold, P = 0.022, in DBA/2N mice). Butyrate or TGF-β alone inhibited cell growth and induced cell cycle arrest. The combined treatment of butyrate and TGF-β synergistically induced cell cycle arrest and apoptosis in RIE-1 cells and repressed Id2 and Id3 levels. Furthermore, knockdown of Id2 gene expression by use of small interfering RNA caused cell cycle arrest and apoptosis. We conclude that dietary fiber pectin enhanced Smad3 expression and activation in the gut. Butyrate and TGF-β induced cell cycle arrest and apoptosis, which may be mediated by repression of Id2. Our results implicate a novel mechanism of dietary fiber in reducing the risk of colorectal cancer development.
authors: Department of Surgery, University of Texas Health Science Center at Houston, 77026, USA.
authors: Yanna
authors: Y
authors: Cao
authors: Xuxia
authors: X
authors: Gao
authors: Weili
authors: W
authors: Zhang
authors: Guohua
authors: G
authors: Zhang
authors: Anthony K
authors: AK
authors: Nguyen
authors: Xianghua
authors: X
authors: Liu
authors: Fernando
authors: F
authors: Jimenez
authors: Charles S
authors: CS
authors: Cox
authors: Courtney M
authors: CM
authors: Townsend
authors: Tien C
authors: TC
authors: Ko
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002087:Butyrates / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D004043:Dietary Fiber / Q000494:pharmacology*; D041981:Gastrointestinal Tract / Q000187:drug effects* / Q000378:metabolism; D051797:Inhibitor of Differentiation Protein 2 / Q000378:metabolism; D051796:Inhibitor of Differentiation Proteins / Q000378:metabolism; D008297:Male; D051379:Mice; D010368:Pectins / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects*; D051900:Smad3 Protein / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: D002087:Butyrates; D004043:Dietary Fiber; C497452:Idb2 protein, mouse; D051797:Inhibitor of Differentiation Protein 2; D051796:Inhibitor of Differentiation Proteins; D034741:RNA, Small Interfering; D051900:Smad3 Protein; C497791:Smad3 protein, mouse; D016212:Transforming Growth Factor beta; C067679:Idb3 protein, mouse; D010368:Pectins