Matches in SemOpenAlex for { <https://semopenalex.org/work/W2110366604> ?p ?o ?g. }
- W2110366604 endingPage "37308" @default.
- W2110366604 startingPage "37296" @default.
- W2110366604 abstract "Factors regulating the proliferation and apoptosis of intestinal stem cells (ISCs) remain incompletely understood. Because ISCs exist among microbial ligands, immune receptors such as toll-like receptor 4 (TLR4) could play a role. We now hypothesize that ISCs express TLR4 and that the activation of TLR4 directly on the intestinal stem cells regulates their ability to proliferate or to undergo apoptosis. Using flow cytometry and fluorescent in situ hybridization for the intestinal stem cell marker Lgr5, we demonstrate that TLR4 is expressed on the Lgr5-positive intestinal stem cells. TLR4 activation reduced proliferation and increased apoptosis in ISCs both in vivo and in ISC organoids, a finding not observed in mice lacking TLR4 in the Lgr5-positive ISCs, confirming the in vivo significance of this effect. To define molecular mechanisms involved, TLR4 inhibited ISC proliferation and increased apoptosis via the p53-up-regulated modulator of apoptosis (PUMA), as TLR4 did not affect crypt proliferation or apoptosis in organoids or mice lacking PUMA. In vivo effects of TLR4 on ISCs required TIR-domain-containing adapter-inducing interferon-β (TRIF) but were independent of myeloid-differentiation primary response-gene 88 (MYD88) and TNFα. Physiological relevance was suggested, as TLR4 activation in necrotizing enterocolitis led to reduced proliferation and increased apoptosis of the intestinal crypts in a manner that could be reversed by inhibition of PUMA, both globally or restricted to the intestinal epithelium. These findings illustrate that TLR4 is expressed on ISCs where it regulates their proliferation and apoptosis through activation of PUMA and that TLR4 regulation of ISCs contributes to the pathogenesis of necrotizing enterocolitis." @default.
- W2110366604 created "2016-06-24" @default.
- W2110366604 creator A5009483775 @default.
- W2110366604 creator A5013062798 @default.
- W2110366604 creator A5025091268 @default.
- W2110366604 creator A5029058133 @default.
- W2110366604 creator A5029781468 @default.
- W2110366604 creator A5041622853 @default.
- W2110366604 creator A5042211554 @default.
- W2110366604 creator A5045670816 @default.
- W2110366604 creator A5047615764 @default.
- W2110366604 creator A5052936626 @default.
- W2110366604 creator A5060860879 @default.
- W2110366604 creator A5070451802 @default.
- W2110366604 creator A5070494686 @default.
- W2110366604 creator A5081486163 @default.
- W2110366604 creator A5083298871 @default.
- W2110366604 creator A5084193552 @default.
- W2110366604 date "2012-10-01" @default.
- W2110366604 modified "2023-10-15" @default.
- W2110366604 title "Toll-like Receptor 4 Is Expressed on Intestinal Stem Cells and Regulates Their Proliferation and Apoptosis via the p53 Up-regulated Modulator of Apoptosis" @default.
- W2110366604 cites W1676263233 @default.
- W2110366604 cites W1874198492 @default.
- W2110366604 cites W1908766372 @default.
- W2110366604 cites W1947770621 @default.
- W2110366604 cites W1965157206 @default.
- W2110366604 cites W1966895787 @default.
- W2110366604 cites W1967535083 @default.
- W2110366604 cites W1971058409 @default.
- W2110366604 cites W1976662817 @default.
- W2110366604 cites W1981209922 @default.
- W2110366604 cites W1981334287 @default.
- W2110366604 cites W1982603620 @default.
- W2110366604 cites W1988983881 @default.
- W2110366604 cites W1989106906 @default.
- W2110366604 cites W1993677820 @default.
- W2110366604 cites W1994216131 @default.
- W2110366604 cites W2003299661 @default.
- W2110366604 cites W2009756725 @default.
- W2110366604 cites W2017218715 @default.
- W2110366604 cites W2026343585 @default.
- W2110366604 cites W2030791386 @default.
- W2110366604 cites W2042492740 @default.
- W2110366604 cites W2049064036 @default.
- W2110366604 cites W2058172887 @default.
- W2110366604 cites W2062004524 @default.
- W2110366604 cites W2069916625 @default.
- W2110366604 cites W2089082314 @default.
- W2110366604 cites W2094534259 @default.
- W2110366604 cites W2096152150 @default.
- W2110366604 cites W2097005995 @default.
- W2110366604 cites W2104081204 @default.
- W2110366604 cites W2105575647 @default.
- W2110366604 cites W2109601788 @default.
- W2110366604 cites W2113234505 @default.
- W2110366604 cites W2121453706 @default.
- W2110366604 cites W2124297826 @default.
- W2110366604 cites W2129319296 @default.
- W2110366604 cites W2133462434 @default.
- W2110366604 cites W2135279653 @default.
- W2110366604 cites W2135435030 @default.
- W2110366604 cites W2148134626 @default.
- W2110366604 cites W2152309111 @default.
- W2110366604 cites W2163194273 @default.
- W2110366604 cites W2165122599 @default.
- W2110366604 cites W2168144313 @default.
- W2110366604 cites W2171977041 @default.
- W2110366604 cites W4235469056 @default.
- W2110366604 doi "https://doi.org/10.1074/jbc.m112.375881" @default.
- W2110366604 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3481327" @default.
- W2110366604 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/22955282" @default.
- W2110366604 hasPublicationYear "2012" @default.
- W2110366604 type Work @default.
- W2110366604 sameAs 2110366604 @default.
- W2110366604 citedByCount "175" @default.
- W2110366604 countsByYear W21103666042013 @default.
- W2110366604 countsByYear W21103666042014 @default.
- W2110366604 countsByYear W21103666042015 @default.
- W2110366604 countsByYear W21103666042016 @default.
- W2110366604 countsByYear W21103666042017 @default.
- W2110366604 countsByYear W21103666042018 @default.
- W2110366604 countsByYear W21103666042019 @default.
- W2110366604 countsByYear W21103666042020 @default.
- W2110366604 countsByYear W21103666042021 @default.
- W2110366604 countsByYear W21103666042022 @default.
- W2110366604 countsByYear W21103666042023 @default.
- W2110366604 crossrefType "journal-article" @default.
- W2110366604 hasAuthorship W2110366604A5009483775 @default.
- W2110366604 hasAuthorship W2110366604A5013062798 @default.
- W2110366604 hasAuthorship W2110366604A5025091268 @default.
- W2110366604 hasAuthorship W2110366604A5029058133 @default.
- W2110366604 hasAuthorship W2110366604A5029781468 @default.
- W2110366604 hasAuthorship W2110366604A5041622853 @default.
- W2110366604 hasAuthorship W2110366604A5042211554 @default.
- W2110366604 hasAuthorship W2110366604A5045670816 @default.
- W2110366604 hasAuthorship W2110366604A5047615764 @default.
- W2110366604 hasAuthorship W2110366604A5052936626 @default.
- W2110366604 hasAuthorship W2110366604A5060860879 @default.