J Neurogastroenterol Motil. 2016 Jul 30;22(3):367-82. doi: 10.5056/jnm16023.
Stem Cells in the Intestine: Possible Roles in Pathogenesis of Irritable Bowel Syndrome.
Journal of neurogastroenterology and motility
Sutheera Ratanasirintrawoot, Nipan Israsena
Affiliations
Affiliations
- Stem Cell and Cell Therapy Research Unit, Chulalongkorn University, Bangkok, Thailand.
- Department of Research Affairs, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
- Department of Pharmacology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
PMID: 27184041
PMCID: PMC4930294 DOI: 10.5056/jnm16023
Abstract
Irritable bowel syndrome is one of the most common functional gastrointestinal (GI) disorders that significantly impair quality of life in patients. Current available treatments are still not effective and the pathophysiology of this condition remains unclearly defined. Recently, research on intestinal stem cells has greatly advanced our understanding of various GI disorders. Alterations in conserved stem cell regulatory pathways such as Notch, Wnt, and bone morphogenic protein/TGF- β have been well documented in diseases such as inflammatory bowel diseases and cancer. Interaction between intestinal stem cells and various signals from their environment is important for the control of stem cell self-renewal, regulation of number and function of specific intestinal cell types, and maintenance of the mucosal barrier. Besides their roles in stem cell regulation, these signals are also known to have potent effects on immune cells, enteric nervous system and secretory cells in the gut, and may be responsible for various aspects of pathogenesis of functional GI disorders, including visceral hypersensitivity, altered gut motility and low grade gut inflammation. In this article, we briefly summarize the components of these signaling pathways, how they can be modified by extrinsic factors and novel treatments, and provide evidenced support of their roles in the inflammation processes. Furthermore, we propose how changes in these signals may contribute to the symptom development and pathogenesis of irritable bowel syndrome.
Keywords: Intestinal stem cells; Irritable bowel syndrome; Notch; Transforming growth factor beta; Wnt
References
- Annu Rev Physiol. 2013;75:289-311 - PubMed
- Cell. 2012 Jul 20;150(2):351-65 - PubMed
- Nat Med. 2012 Mar 11;18(4):618-23 - PubMed
- Gastroenterology. 2006 Jul;131(1):117-29 - PubMed
- Clin Exp Immunol. 2003 Oct;134(1):120-6 - PubMed
- Neurogastroenterol Motil. 2014 Mar;26(3):296-302 - PubMed
- Science. 2012 Oct 5;338(6103):108-13 - PubMed
- Nature. 2013 Nov 14;503(7475):272-6 - PubMed
- World J Gastroenterol. 2015 Jul 7;21(25):7621-36 - PubMed
- J Pathol. 2015 Oct;237(2):135-45 - PubMed
- Nature. 2011 Jun 15;474(7351):307-17 - PubMed
- World J Gastroenterol. 2014 Mar 14;20(10):2456-69 - PubMed
- Development. 2012 Mar;139(6):1071-82 - PubMed
- World J Gastroenterol. 2014 Jul 21;20(27):8807-20 - PubMed
- Cell Stem Cell. 2013 Dec 5;13(6):734-44 - PubMed
- Mol Cell Biol. 2000 May;20(9):3292-307 - PubMed
- Mol Neurobiol. 2016 Jan;53(1):299-309 - PubMed
- Science. 2001 Dec 7;294(5549):2155-8 - PubMed
- Gastroenterology. 2008 Mar;134(3):849-64 - PubMed
- Gastroenterology. 2011 Apr;140(4):1230-1240.e1-7 - PubMed
- Cell Tissue Res. 2006 Jun;324(3):353-60 - PubMed
- J Clin Invest. 2011 Sep;121(9):3412-24 - PubMed
- Cell Cycle. 2004 May;3(5):554-7 - PubMed
- Nature. 2007 Oct 25;449(7165):1003-7 - PubMed
- Nat Genet. 1998 Aug;19(4):379-83 - PubMed
- J Immunol. 2008 Oct 1;181(7):4441-5 - PubMed
- Front Immunol. 2015 Jun 18;6:319 - PubMed
- EMBO Rep. 2008 Apr;9(4):377-83 - PubMed
- Neurogastroenterol Motil. 2013 Jul;25(7):601-e464 - PubMed
- Eur J Pain. 2012 Nov;16(10):1444-54 - PubMed
- Am J Transplant. 2009 Jul;9(7):1620-8 - PubMed
- Mucosal Immunol. 2016 Jul;9(4):986-98 - PubMed
- J Clin Invest. 2009 Jun;119(6):1420-8 - PubMed
- Am J Physiol Gastrointest Liver Physiol. 2013 Jul 1;305(1):G1-24 - PubMed
- Diabetes Obes Metab. 2011 Oct;13 Suppl 1:5-12 - PubMed
- Mucosal Immunol. 2008 Nov;1 Suppl 1:S50-3 - PubMed
- Int J Obes (Lond). 2014 Nov;38(11):1440-8 - PubMed
- Am J Physiol Gastrointest Liver Physiol. 2009 Jun;296(6):G1332-43 - PubMed
- Nat Rev Mol Cell Biol. 2012 Oct;13(10):616-30 - PubMed
- Development. 2000 Aug;127(16):3533-42 - PubMed
- Nat Cell Biol. 2012 Oct;14(10):1099-104 - PubMed
- Cell Tissue Kinet. 1974 May;7(3):271-83 - PubMed
- J Clin Invest. 2015 Mar 2;125(3):949-55 - PubMed
- Gastroenterology. 2007 Sep;133(3):887-96 - PubMed
- Scand J Gastroenterol. 2006 Feb;41(2):170-7 - PubMed
- J Gastroenterol. 2016 Jan;51(1):11-21 - PubMed
- Annu Rev Physiol. 2013;75:263-88 - PubMed
- Mol Cell Biol. 2009 Nov;29(21):5679-95 - PubMed
- Genes Dev. 2003 Jul 15;17(14):1709-13 - PubMed
- Exp Cell Res. 2011 Jul 1;317(11):1640-8 - PubMed
- Curr Biol. 2004 Feb 3;14 (3):R129-38 - PubMed
- J Clin Invest. 2001 Aug;108(4):523-6 - PubMed
- Nature. 2001 May 31;411(6837):603-6 - PubMed
- Gastroenterology. 2007 Mar;132(3):913-20 - PubMed
- Science. 2004 Mar 12;303(5664):1684-6 - PubMed
- N Engl J Med. 2015 Mar 19;372(12):1104-13 - PubMed
- EMBO Rep. 2015 May;16(5):571-81 - PubMed
- PLoS One. 2012;7(6):e38965 - PubMed
- J Cell Physiol. 2015 May;230(5):969-81 - PubMed
- Nat Rev Mol Cell Biol. 2014 Jan;15(1):19-33 - PubMed
- Mol Cell Neurosci. 2015 Sep;68:24-35 - PubMed
- Mol Med Rep. 2013 Apr;7(4):1081-5 - PubMed
- Am J Anat. 1981 Jan;160(1):77-91 - PubMed
- Genome Biol. 2012;13(3):242 - PubMed
- J Physiol. 2014 Jul 15;592(14):2959-65 - PubMed
- Curr Stem Cell Res Ther. 2015;10(6):499-508 - PubMed
- Gut. 2013 Oct;62(10):1456-65 - PubMed
- J Neuroinflammation. 2015 Feb 03;12:23 - PubMed
- Oncogene. 2008 Sep 1;27(38):5148-67 - PubMed
- Nature. 2005 Jun 16;435(7044):959-63 - PubMed
- Trends Cell Biol. 2015 Feb;25(2):100-8 - PubMed
- Nature. 2011 Jan 20;469(7330):415-8 - PubMed
- Nature. 2015 Dec 24;528(7583):560-4 - PubMed
- Nature. 2011 Jul 04;476(7360):293-7 - PubMed
- Genes Dev. 2005 Oct 15;19(20):2412-7 - PubMed
- Am J Physiol Gastrointest Liver Physiol. 2012 May 15;302(10):G1151-62 - PubMed
- Cell Mol Life Sci. 2015 Oct;72(20):3883-96 - PubMed
- Nat Rev Gastroenterol Hepatol. 2015 Jan;12(1):36-49 - PubMed
- Cell. 2008 Nov 28;135(5):825-37 - PubMed
- Science. 2011 Dec 9;334(6061):1420-4 - PubMed
- Int J Mol Med. 2014 Aug;34(2):363-71 - PubMed
- Gastroenterology. 2008 Jan;134(1):192-203 - PubMed
- Gastroenterology. 2003 Dec;125(6):1651-9 - PubMed
- J Clin Invest. 2001 Aug;108(4):601-9 - PubMed
- Gastroenterology. 2005 Aug;129(2):626-38 - PubMed
- Gastroenterology. 2014 Oct;147(4):822-834.e13 - PubMed
- PLoS Comput Biol. 2015 Aug 19;11(8):e1004285 - PubMed
- Nat Rev Neurosci. 2010 Feb;11(2):77-86 - PubMed
- Cell Stem Cell. 2014 Feb 6;14(2):149-59 - PubMed
- Nat Genet. 2004 Oct;36(10 ):1117-21 - PubMed
- Development. 2015 Feb 15;142(4):654-64 - PubMed
- World J Gastroenterol. 2014 Aug 28;20(32):11273-80 - PubMed
- PLoS Med. 2008 Mar 4;5(3):e54 - PubMed
- PeerJ. 2014 May 01;2:e370 - PubMed
- Immunity. 2010 Mar 26;32(3):392-402 - PubMed
- Gastroenterology. 2006 Jan;130(1):34-43 - PubMed
- Am J Physiol Gastrointest Liver Physiol. 2014 Sep 1;307(5):G487-98 - PubMed
- J Clin Invest. 2011 Sep;121(9):3398-411 - PubMed
- Prog Neurobiol. 2008 Nov;86(3):281-96 - PubMed
- Nat Rev Gastroenterol Hepatol. 2010 Mar;7(3):163-73 - PubMed
- Nature. 2011 Jun 15;474(7351):298-306 - PubMed
- Diabetes. 2001 May;50(5):928-36 - PubMed
- Neurogastroenterol Motil. 2012 Jun;24(6):560-5, e254-5 - PubMed
- Digestion. 2015 ;92 (2):73-7 - PubMed
- Am J Physiol Gastrointest Liver Physiol. 2011 Jun;300(6):G1065-79 - PubMed
- Int J Mol Med. 2009 Jan;23 (1):41-8 - PubMed
- Development. 2014 Jun;141(11):2206-15 - PubMed
- EMBO J. 2014 Sep 17;33(18):2057-68 - PubMed
- J Neurogastroenterol Motil. 2011 Oct;17(4):349-59 - PubMed
- Inflamm Bowel Dis. 2011 Jan;17(1):213-20 - PubMed
- J Nutr Biochem. 2012 Oct;23 (10 ):1207-13 - PubMed
- Trends Genet. 2015 Jun;31(6):344-51 - PubMed
- Cell. 2009 Mar 6;136(5):903-12 - PubMed
- BMC Syst Biol. 2009 Jul 17;3:73 - PubMed
- Clin Cancer Res. 2006 Sep 15;12(18):5403-10 - PubMed
- J Gastroenterol Hepatol. 2011 Apr;26 Suppl 3:67-72 - PubMed
- Proc Natl Acad Sci U S A. 2014 Mar 4;111(9):3472-7 - PubMed
- EMBO Rep. 2012 Aug;13(8):684-98 - PubMed
- Mucosal Immunol. 2014 Jul;7(4):995-1005 - PubMed
- Infect Immun. 2014 Jul;82(7):2680-7 - PubMed
- Cell Stem Cell. 2015 Feb 5;16(2):158-70 - PubMed
- Nature. 2001 May 31;411(6837):599-603 - PubMed
- Cell Stem Cell. 2012 Dec 7;11(6):751-64 - PubMed
- Gastroenterology. 2006 Dec;131(6):1786-98 - PubMed
- J Gastroenterol. 2015 May;50(5):495-507 - PubMed
- Gut. 2007 Jul;56(7):949-57 - PubMed
- Gastroenterology. 2011 Jul;141(1):259-68, 268.e1-8 - PubMed
- J Gastroenterol. 2010 Jun;45(6):608-17 - PubMed
- Mol Cell Biol. 2012 May;32(10):1918-27 - PubMed
- J Immunol. 2012 Mar 1;188(5):2427-36 - PubMed
- Nature. 2009 May 14;459(7244):262-5 - PubMed
- Clin Transl Gastroenterol. 2012 Apr 26;3:e13 - PubMed
- Cell Rep. 2015 Apr 7;11(1):33-42 - PubMed
- Inflamm Bowel Dis. 2015 Dec;21(12):2921-5 - PubMed
- Dev Biol. 2005 Sep 1;285(1):101-15 - PubMed
- Digestion. 2008;78(2-3):72-6 - PubMed
- Gut Liver. 2015 May 23;9(3):318-31 - PubMed
- Am J Gastroenterol. 2012 Jun;107(6):891-9 - PubMed
- N Engl J Med. 2006 Jul 20;355(3):270-80 - PubMed
- Aliment Pharmacol Ther. 2007 Aug 15;26(4):535-44 - PubMed
- Neuron. 2014 Jul 2;83(1):104-21 - PubMed
- Gastroenterology. 2008 Sep;135(3):849-60, 860.e1-6 - PubMed
- Nat Med. 2015 Jan;21(1):62-70 - PubMed
- Science. 1996 Mar 29;271(5257):1826-32 - PubMed
- Dev Biol. 2010 Oct 15;346(2):215-23 - PubMed
- Dev Biol. 2007 Sep 15;309(2):298-305 - PubMed
- Am J Anat. 1981 Jan;160(1):51-63 - PubMed
- Proc Natl Acad Sci U S A. 2007 Jul 3;104(27):11328-33 - PubMed
- Am J Physiol Gastrointest Liver Physiol. 2009 Jan;296(1):G23-35 - PubMed
- Proc Natl Acad Sci U S A. 2007 Sep 25;104(39):15418-23 - PubMed
- Curr Drug Targets. 2008 Jul;9(7):565-70 - PubMed
- Gastroenterology. 1993 Nov;105(5):1323-32 - PubMed
- Br J Pharmacol. 2011 Jan;162(1):18-37 - PubMed
- Mucosal Immunol. 2015 Jul;8(4):712-9 - PubMed
- Genes Dev. 1998 Mar 15;12(6):820-30 - PubMed
- Anat Rec. 1948 Mar;100(3):357-77 - PubMed
- Nature. 2013 Mar 7;495(7439):65-9 - PubMed
- PLoS One. 2012;7(5):e36449 - PubMed
Publication Types