ELIZA

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288503 occurrences (No.86 in the rank) during 5 years in the PubMed. [cache]

26) Here, we examine the role of TGFβ signaling via SMAD4 in modulation of colon barrier function.

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PMID:33759564 DOI:10.1152/ajpgi.00053.2021

2021 American journal of physiology. Gastrointestinal and liver physiology

* Colon epithelial cell TGFβ signaling modulates the expression of tight junction proteins and barrier function in mice.

- Defective barrier function is a predisposing factor in inflammatory bowel disease (IBD) and colitis-associated cancer (CAC). Although TGFβ signaling defects have been associated with IBD and CAC, few studies have examined the relationship between TGFβ and intestinal barrier function. Here, we examine the role of TGFβ signaling via SMAD4 in modulation of colon barrier function. The Smad4 gene was conditionally deleted in the intestines of adult mice and intestinal permeability assessed using an in vivo 4 kDa FITC-Dextran (FD4) permeability assay. Mouse colon was isolated for gene expression (RNA-sequencing), Western blot, and immunofluorescence analysis. In vitro colon organoid culture was utilized to assess junction-related gene expression by qPCR and transepithelial resistance (TER). In silico analyses of human IBD and colon cancer databases were performed. Mice lacking intestinal expression of Smad4 demonstrate increased colonic permeability to FD4 without gross mucosal damage. mRNA/protein expression analyses demonstrate significant increases in Cldn2/Claudin 2 and Cldn8/Claudin 8, and decreases in Cldn3, Cldn4, and Cldn7/Claudin 7 with intestinal SMAD4 loss in vivo without changes in Claudin protein localization. TGFβ1/BMP2 treatment of polarized SMAD4+ colonoids increases TER. Cldn2, Cldn4, Cldn7, and Cldn8 are regulated by canonical TGFβ signaling, and TGFβ-dependent regulation of these genes is dependent on nascent RNA transcription (Cldn2, Cldn4, Cldn8) but not nascent protein translation (Cldn4, Cldn8). Human IBD/colon cancer specimens demonstrate decreased SMAD4, CLDN4, CLDN7, and CLDN8 and increased CLDN2 compared with healthy controls. Canonical TGFβ signaling modulates the expression of tight junction proteins and barrier function in mouse colon.NEW & NOTEWORTHY We demonstrate that canonical TGFβ family signaling modulates the expression of critical tight junction proteins in colon epithelial cells, and that expression of these tight junction proteins is associated with maintenance of colon epithelial barrier function in mice.

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(1)86 null	(9)5 following	(17)3 mutations	(25)2 for
(2)72 of	(10)5 was	(18)3 not	(26)2 have
(3)68 and	(11)5 with	(19)3 were	(27)2 including
(4)63 in	(12)4 by	(20)3 which	(28)2 measures
(5)16 is	(13)4 has	(21)2 after	(29)2 or
(6)13 as	(14)4 tests	(22)2 among	(30)2 quality
(7)5 are	(15)4 to	(23)2 data	(31)2 that
(8)5 associated	(16)3 at	(24)2 during	(32)2 variants

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--- WordNet output for function --- =>1.機能, 関数, 役割, 働き, 2.機能する, 作用する, 働く, 役目を果たす, 3.社交的会合, パーティー, 儀式 Overview of noun function The noun function has 7 senses (first 3 from tagged texts) 1. (43) function, mathematical function, single-valued function, map, mapping -- ((mathematics) a mathematical relation such that each element of a given set (the domain of the function) is associated with an element of another set (the range of the function)) 2. (24) function, purpose, role, use -- (what something is used for; "the function of an auger is to bore holes"; "ballet is beautiful but what use is it?") 3. (7) function, office, part, role -- (the actions and activities assigned to or required or expected of a person or group; "the function of a teacher"; "the government must do its part"; "play its role") 4. function -- (a relation such that one thing is dependent on another; "height is a function of age"; "price is a function of supply and demand") 5. function -- (a formal or official social gathering or ceremony; "it was a black-tie function") 6. affair, occasion, social occasion, function, social function -- (a vaguely specified social event; "the party was quite an affair"; "an occasion arranged to honor the president"; "a seemingly endless round of social functions") 7. routine, subroutine, subprogram, procedure, function -- (a set sequence of steps, part of larger computer program) Overview of verb function The verb function has 3 senses (first 3 from tagged texts) 1. (9) function, work, operate, go, run -- (perform as expected when applied; "The washing machine won't go unless it's plugged in"; "Does this old car still run well?"; "This old radio doesn't work anymore") 2. (3) serve, function -- (serve a purpose, role, or function; "The tree stump serves as a table"; "The female students served as a control group"; "This table would serve very well"; "His freedom served him well"; "The table functions as a desk") 3. (1) officiate, function -- (perform duties attached to a particular office or place or function; "His wife officiated as his private secretary") --- WordNet end ---