FAM3D is essential for colon homeostasis and host defense against inflammation associated carcinogenesis

Nature Communications
Weiwei LiangYing Wang

Abstract

The physiological homeostasis of gut mucosal barrier is maintained by both genetic and environmental factors and its impairment leads to pathogenesis such as inflammatory bowel disease. A cytokine like molecule, FAM3D (mouse Fam3D), is highly expressed in mouse gastrointestinal tract. Here, we demonstrate that deficiency in Fam3D is associated with impaired integrity of colonic mucosa, increased epithelial hyper-proliferation, reduced anti-microbial peptide production and increased sensitivity to chemically induced colitis associated with high incidence of cancer. Pretreatment of Fam3D-/- mice with antibiotics significantly reduces the severity of chemically induced colitis and wild type (WT) mice co-housed with Fam3D-/- mice phenocopy Fam3D-deficiency showing increased sensitivity to colitis and skewed composition of fecal microbiota. An initial equilibrium of microbiota in cohoused WT and Fam3D-/- mice is followed by an increasing divergence of the bacterial composition after separation. These results demonstrate the essential role of Fam3D in colon homeostasis, protection against inflammation associated cancer and normal microbiota composition.

References

Nov 1, 2000·Cell·M Bienz, H Clevers
Jun 8, 2001·The American Journal of Clinical Nutrition·B Deplancke, H R Gaskins
Sep 17, 2004·Cell·Hans Clevers
Apr 5, 2007·Nature Protocols·Stefan WirtzMarkus F Neurath
Dec 7, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Brian A BabbinAsma Nusrat
Sep 23, 2008·Proceedings of the National Academy of Sciences of the United States of America·Malin E V JohanssonGunnar C Hansson
Apr 1, 2009·Journal of Carcinogenesis·Takuji Tanaka
Jun 11, 2010·Proceedings of the National Academy of Sciences of the United States of America·J Gregory CaporasoRob Knight
Nov 3, 2010·The American Journal of Pathology·Christy C WentworthAndrew S Neish
Dec 15, 2010·Nature Reviews. Immunology·Maya Saleh, Giorgio Trinchieri
Mar 9, 2011·The Journal of Clinical Investigation·Jianxin FuLijun Xia
Jun 17, 2011·Nature·Kevin J Maloy, Fiona Powrie
Jan 10, 2012·The Journal of Nutritional Biochemistry·Nicole J W de WitRoelof van der Meer
Nov 30, 2012·Nucleic Acids Research·Christian QuastFrank Oliver Glöckner
Dec 18, 2012·The Journal of Clinical Investigation·Giovanna LeoniAsma Nusrat
Feb 9, 2013·Science·Sebastian E WinterAndreas J Bäumler
Mar 5, 2013·The Journal of Clinical Investigation·Keqiang ChenJi Ming Wang
Oct 15, 2013·Cancer Discovery·Matthew J EllisUNKNOWN Clinical Proteomic Tumor Analysis Consortium (CPTAC)
Nov 28, 2013·GigaScience·Yoshiki Vázquez-BaezaRob Knight
Feb 26, 2014·Nature Reviews. Immunology·Lance W Peterson, David Artis
Apr 16, 2015·Journal of Proteome Research·Nathan J EdwardsKaren A Ketchum
May 24, 2016·Nature Methods·Benjamin J CallahanSusan P Holmes
Jul 22, 2017·Neoplasia : an International Journal for Oncology Research·Darshan S ChandrashekarSooryanarayana Varambally
Aug 19, 2017·Science·Mathias UhlenFredrik Ponten

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Methods Mentioned

BETA
IECs
PCR
confocal microscopy
RNA-seq
FACS
transfection
Fluorescence
fluorescence-activated cell sorting

Software Mentioned

ImageJ
HTSeq
GraphPad Prism
FlowJo
QIIME2
PERL script Perl Archive Network ( CPAN ) Statistics TTest
Image J
GSEA
edgeR
TopHat2

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