title: Shigella dysenteriae modulates BMP pathway to induce mucin gene expression in vivo and in vitro.
abstract: Mucosal epithelial cells in the intestine act as the first line of host defense against pathogens by increasing mucin production for clearance. Despite this fact, the underlying molecular mechanisms by which Shigella dysenteriae transduce mucin gene expression remain poorly defined. The goal of this study was to determine the role of Bone morphogenetic protein (BMP) pathway in mucin gene expression during S. dysenteriae infection. In this study we demonstrate that S. dysenteriae activates BMP signaling to induce MUC2 and MUC5AC gene expression in rat ileal loop model and in vitro. We also observed that BMP pathway regulates CDX2 expression which plays a critical role in induction of MUC2 gene during S. dysenteriae infection. In SMAD4 silenced cells S. dysenteriae infection did not abrogate MUC2 and MUC5AC gene expression whereas in CDX2 silenced cells it induces differential expression of MUC5AC gene. These results suggest that SMAD4-CDX2 induces MUC2 gene expression whereas SMAD4 directly influences differential expression of MUC5AC gene. Altogether, our results show that during S. dysenteriae infection the BMP pathway modulates inflammatory transcription factors CDX2 and SMAD4 to induce MUC2 and MUC5AC gene expression which plays a key role in the regulation of host mucosal defense thereby paving a cue for therapeutic application.
authors.affiliation: Unit of Biochemistry, Department of Zoology, School of Life Sciences, University of Madras, Guindy Campus, Chennai, Tamilnadu, India.
authors.forename: Ashidha
authors.initials: A
authors.lastname: Gopal
authors.affiliation: Unit of Biochemistry, Department of Zoology, School of Life Sciences, University of Madras, Guindy Campus, Chennai, Tamilnadu, India.
authors.forename: Soumya Chidambaram
authors.initials: SC
authors.lastname: Iyer
authors.affiliation: Department of Pathology, Duke University Medical Center, Durham, North Carolina, United States of America.
authors.forename: Udhayakumar
authors.initials: U
authors.lastname: Gopal
authors.affiliation: Department of Biochemistry, University of Madras, Guindy Campus, Chennai, Tamilnadu, India.
authors.forename: Niranjali
authors.initials: N
authors.lastname: Devaraj
authors.affiliation: Unit of Biochemistry, Department of Zoology, School of Life Sciences, University of Madras, Guindy Campus, Chennai, Tamilnadu, India.
authors.forename: Devaraj
authors.initials: D
authors.lastname: Halagowder
mesh_terms: D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D000071616:CDX2 Transcription Factor; D002460:Cell Line; D004195:Disease Models, Animal; D004405:Dysentery, Bacillary / Q000235:genetics* / Q000378:metabolism* / Q000382:microbiology; D005786:Gene Expression Regulation; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007079:Ileitis / Q000235:genetics / Q000378:metabolism / Q000382:microbiology; D008297:Male; D055271:Mucin 5AC / Q000096:biosynthesis / Q000235:genetics; D009077:Mucins / Q000096:biosynthesis / Q000235:genetics*; D051381:Rats; D012762:Shigella dysenteriae; D015398:Signal Transduction; D051901:Smad4 Protein / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D019485:Bone Morphogenetic Proteins; D000071616:CDX2 Transcription Factor; C541055:Cdx2 protein, rat; D018398:Homeodomain Proteins; D055271:Mucin 5AC; D009077:Mucins; D051901:Smad4 Protein; D014157:Transcription Factors