ArticleAmerican journal of physiology. Gastrointestinal and liver physiology2009
Inflammation-induced, 3'UTR-dependent translational inhibition of Hsp70 mRNA impairs intestinal homeostasis.
Article in American journal of physiology. Gastrointestinal and liver physiology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 31 citations in OpenAlex.
- Intracellular heat shock protein-70 negatively regulates TLR4 signaling in the newborn intestinal epithelium.Journal of immunology (Baltimore, Md. : 1950) · 2012Trial
- NFAT5 dictates crosstalk between intestinal epithelial regenerative capacity and microbiota in murine colitis models.The Journal of clinical investigation · 2025Article
- Review
- The Functions and Therapeutic Potential of Heat Shock Proteins in Inflammatory Bowel Disease-An Update.International journal of molecular sciences · 2019Review
- Impact of Toll-Like Receptor 4 Signaling in Necrotizing Enterocolitis: The State of the Science.Clinics in perinatology · 2019Review
- Distinct roles of intracellular heat shock protein 70 in maintaining gastrointestinal homeostasis.American journal of physiology. Gastrointestinal and liver physiology · 2018Article
- Soluble bioactive microbial mediators regulate proteasomal degradation and autophagy to protect against inflammation-induced stress.American journal of physiology. Gastrointestinal and liver physiology · 2016Article
- Gut epithelial inducible heat-shock proteins and their modulation by diet and the microbiota.Nutrition reviews · 2016Review
- Effects of Lactobacillus johnsonii and Lactobacillus reuteri on gut barrier function and heat shock proteins in intestinal porcine epithelial cells.Physiological reports · 2015Article
- Heat Shock Proteins: Intestinal Gatekeepers that Are Influenced by Dietary Components and the Gut Microbiota.Pathogens (Basel, Switzerland) · 2014Review
- Therapeutic treatment with a novel hypoxia-inducible factor hydroxylase inhibitor (TRC160334) ameliorates murine colitis.Clinical and experimental gastroenterology · 2014Article
- RNA interference links oxidative stress to the inhibition of heat stress adaptation.Antioxidants & redox signaling · 2012Article
- Epicatechin used in the treatment of intestinal inflammatory disease: an analysis by experimental models.Evidence-based complementary and alternative medicine : eCAM · 2012Article
- Polyamines mediate glutamine-dependent induction of the intestinal epithelial heat shock response.American journal of physiology. Gastrointestinal and liver physiology · 2011Article
- Nanoparticle-based therapeutic delivery of prohibitin to the colonic epithelial cells ameliorates acute murine colitis.Inflammatory bowel diseases · 2011Article
- Mother's milk-induced Hsp70 expression preserves intestinal epithelial barrier function in an immature rat pup model.Pediatric research · 2011Article
- Regional differences in colonic mucosa-associated microbiota determine the physiological expression of host heat shock proteins.American journal of physiology. Gastrointestinal and liver physiology · 2010Article
- Regional mucosa-associated microbiota determine physiological expression of TLR2 and TLR4 in murine colon.PloS one · 2010Article
- Stress granule formation mediates the inhibition of colonic Hsp70 translation by interferon-gamma and tumor necrosis factor-alpha.American journal of physiology. Gastrointestinal and liver physiology · 2010Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Although the inducible heat shock protein 70 (Hsp70) is essential for maintaining intestinal homeostasis in colitis, it is translationally downregulated in inflamed colonic mucosa, paradoxically rendering the gut more susceptible to injury. We examined the basis for this process by analyzing the role of untranslated regions (UTR) of Hsp70 mRNA in inflammation-associated downregulation in vitro and in vivo. Using luciferase-reporter assays in young adult mouse intestinal epithelial cells, we determined that cytokine-induced translational inhibition of Hsp70 mRNA was mediated by the 3'UTR, but not 5'UTR. In vivo, dextran sodium sulfate (DSS) colitis was induced in wild-type (WT) and villin-promoter regulated "UTR-less" Hsp70 transgenic (TG) mice, the latter exhibiting intestinal epithelial-specific transgene expression. Progressive downregulation of colonic Hsp70 protein expression was observed in WT, but not in TG, mice with increasing severity of mucosal inflammation, confirming the essential role of the 3'UTR in mediating inflammation-associated downregulation of Hsp70. Hsp70 TG mice demonstrated significantly lower endoscopic and histological inflammation scores in DSS-induced colitis than WT. In conclusion, downregulation of Hsp70 expression in inflamed mucosa is mediated by translational inhibition requiring the 3'UTR, resulting in increased mucosal injury. By forcing intestinal epithelial-specific Hsp70 expression in vivo, the severity of experimentally induced colitis was significantly reduced.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.