Dietary fiber enhances TGF-β signaling and growth inhibition in the gut

Yanna Cao, Xuxia Gao, Weili Zhang, Guohua Zhang, Anthony K. Nguyen, Xianghua Liu, Fernando Jimenez, Charles S. Cox, Courtney Townsend, Tien C. Ko

Research output: Contribution to journalArticle

19 Citations (Scopus)

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-β1, 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-_ 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.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume301
Issue number1
DOIs
StatePublished - Jul 2011

Fingerprint

Butyrates
Dietary Fiber
Cell Cycle Checkpoints
Inbred DBA Mouse
Growth
Apoptosis
Smad3 Protein
Colorectal Neoplasms
Epithelium
Volatile Fatty Acids
Jejunum
Small Interfering RNA
Fermentation
Rodentia
Epithelial Cells
Gene Expression
pectin

Keywords

  • Apoptosis
  • Butyrate
  • Cell cycle arrest
  • Inhibitor of differentiation

ASJC Scopus subject areas

  • Gastroenterology
  • Physiology (medical)
  • Physiology
  • Hepatology

Cite this

Dietary fiber enhances TGF-β signaling and growth inhibition in the gut. / Cao, Yanna; Gao, Xuxia; Zhang, Weili; Zhang, Guohua; Nguyen, Anthony K.; Liu, Xianghua; Jimenez, Fernando; Cox, Charles S.; Townsend, Courtney; Ko, Tien C.

In: American Journal of Physiology - Gastrointestinal and Liver Physiology, Vol. 301, No. 1, 07.2011.

Research output: Contribution to journalArticle

Cao, Yanna ; Gao, Xuxia ; Zhang, Weili ; Zhang, Guohua ; Nguyen, Anthony K. ; Liu, Xianghua ; Jimenez, Fernando ; Cox, Charles S. ; Townsend, Courtney ; Ko, Tien C. / Dietary fiber enhances TGF-β signaling and growth inhibition in the gut. In: American Journal of Physiology - Gastrointestinal and Liver Physiology. 2011 ; Vol. 301, No. 1.
@article{bb274cf7dbae42faba226dad1b32c08a,
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-β1, 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-_ 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.",
keywords = "Apoptosis, Butyrate, Cell cycle arrest, Inhibitor of differentiation",
author = "Yanna Cao and Xuxia Gao and Weili Zhang and Guohua Zhang and Nguyen, {Anthony K.} and Xianghua Liu and Fernando Jimenez and Cox, {Charles S.} and Courtney Townsend and Ko, {Tien C.}",
year = "2011",
month = "7",
doi = "10.1152/ajpgi.00362.2010",
language = "English (US)",
volume = "301",
journal = "American Journal of Physiology - Endocrinology and Metabolism",
issn = "0193-1849",
publisher = "American Physiological Society",
number = "1",

}

TY - JOUR

T1 - Dietary fiber enhances TGF-β signaling and growth inhibition in the gut

AU - Cao, Yanna

AU - Gao, Xuxia

AU - Zhang, Weili

AU - Zhang, Guohua

AU - Nguyen, Anthony K.

AU - Liu, Xianghua

AU - Jimenez, Fernando

AU - Cox, Charles S.

AU - Townsend, Courtney

AU - Ko, Tien C.

PY - 2011/7

Y1 - 2011/7

N2 - 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-β1, 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-_ 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.

AB - 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-β1, 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-_ 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.

KW - Apoptosis

KW - Butyrate

KW - Cell cycle arrest

KW - Inhibitor of differentiation

UR - http://www.scopus.com/inward/record.url?scp=79959824406&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79959824406&partnerID=8YFLogxK

U2 - 10.1152/ajpgi.00362.2010

DO - 10.1152/ajpgi.00362.2010

M3 - Article

VL - 301

JO - American Journal of Physiology - Endocrinology and Metabolism

JF - American Journal of Physiology - Endocrinology and Metabolism

SN - 0193-1849

IS - 1

ER -