NDLI: Inflammation-induced, 3′UTR-dependent translational inhibition of Hsp70 mRNA impairs intestinal homeostasis

Content Provider	PubMed Central
Author	Hu, Shien Zhu, Xiaorong Triggs, Joseph R. Tao, Yun Wang, Yunwei Lichtenstein, Lev Bissonnette, Marc Musch, Mark W. Chang, Eugene B.
Copyright Year	2009
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.
Related Links	http://dx.doi.org/10.1152/ajpgi.00027.2009
Starting Page	1003
File Format	PDF
ISSN	01931857
e-ISSN	15221547
Journal	American Journal of Physiology - Gastrointestinal and Liver Physiology
Issue Number	5
Volume Number	296
Language	English
Publisher	American Physiological Society
Publisher Date	2009-05-01
Access Restriction	Open
Rights Holder	American Physiological Society
Subject Keyword	Hepatology Gastroenterology Physiology (medical) Physiology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Hepatology Physiology Physiology (medical) Gastroenterology

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

Inflammation-induced, 3'UTR-dependent translational inhibition of Hsp70 mRNA impairs intestinal homeostasis.

Hyaluronan in intestinal homeostasis and inflammation: implications for fibrosis

Tumor necrosis factor-alpha impairs intestinal phosphate absorption in colitis

Disruption of retinoblastoma protein expression in the intestinal epithelium impairs lipid absorption

Translational repression of SLC26A3 by miR-494 in intestinal epithelial cells

Immunomodulatory action of dietary fish oil and targeted deletion of intestinal epithelial cell PPARδ in inflammation-induced colon carcinogenesis

Translational inhibition of colonic epithelial heat shock proteins by interferon-gamma and TNF-alpha in intestinal inflammation

Animal models of ischemia-reperfusion-induced intestinal injury: progress and promise for translational research

Transcriptional inhibition of intestinal NHE8 expression by glucocorticoids involves Pax5

Inflammation-induced, 3′UTR-dependent translational inhibition of Hsp70 mRNA impairs intestinal homeostasis

Similar Documents

Inflammation-induced, 3'UTR-dependent translational inhibition of Hsp70 mRNA impairs intestinal homeostasis.

Hyaluronan in intestinal homeostasis and inflammation: implications for fibrosis

Tumor necrosis factor-alpha impairs intestinal phosphate absorption in colitis

Disruption of retinoblastoma protein expression in the intestinal epithelium impairs lipid absorption

Translational repression of SLC26A3 by miR-494 in intestinal epithelial cells

Immunomodulatory action of dietary fish oil and targeted deletion of intestinal epithelial cell PPARδ in inflammation-induced colon carcinogenesis

Translational inhibition of colonic epithelial heat shock proteins by interferon-gamma and TNF-alpha in intestinal inflammation

Animal models of ischemia-reperfusion-induced intestinal injury: progress and promise for translational research

Transcriptional inhibition of intestinal NHE8 expression by glucocorticoids involves Pax5

Inflammation-induced, 3′UTR-dependent translational inhibition of Hsp70 mRNA impairs intestinal homeostasis