title: Angiogenin Mediates Cell-Autonomous Translational Control under Endoplasmic Reticulum Stress and Attenuates Kidney Injury.
abstract: Endoplasmic reticulum (ER) stress is involved in the pathophysiology of kidney disease and aging, but the molecular bases underlying the biologic outcomes on the evolution of renal disease remain mostly unknown. Angiogenin (ANG) is a ribonuclease that promotes cellular adaptation under stress but its contribution to ER stress signaling remains elusive. In this study, we investigated the ANG-mediated contribution to the signaling and biologic outcomes of ER stress in kidney injury. ANG expression was significantly higher in samples from injured human kidneys than in samples from normal human kidneys, and in mouse and rat kidneys, ANG expression was specifically induced under ER stress. In human renal epithelial cells, ER stress induced ANG expression in a manner dependent on the activity of transcription factor XBP1, and ANG promoted cellular adaptation to ER stress through induction of stress granules and inhibition of translation. Moreover, the severity of renal lesions induced by ER stress was dramatically greater in ANG knockout mice (Ang(-/-)) mice than in wild-type mice. These results indicate that ANG is a critical mediator of tissue adaptation to kidney injury and reveal a physiologically relevant ER stress-mediated adaptive translational control mechanism.
authors.affiliation: Institut National de la Sante et de la Recherche Médicale (INSERM) U1147, Saints-Pères Research Center Paris, France; Paris Descartes University Paris, France;
authors.forename: Iadh
authors.initials: I
authors.lastname: Mami
authors.affiliation: Nephrology Department Caen University Hospital, France;
authors.forename: Nicolas
authors.initials: N
authors.lastname: Bouvier
authors.affiliation: Paris Descartes University Paris, France; INSERM U1151, Sick Childrens Necker Institute Paris, France;
authors.forename: Khalil
authors.initials: K
authors.lastname: El Karoui
authors.affiliation: Paris Descartes University Paris, France; INSERM U1151, Sick Childrens Necker Institute Paris, France;
authors.forename: Morgan
authors.initials: M
authors.lastname: Gallazzini
authors.affiliation: Paris Descartes University Paris, France; Pathology Department, Necker Hospital Paris, France;
authors.forename: Marion
authors.initials: M
authors.lastname: Rabant
authors.affiliation: Institut National de la Sante et de la Recherche Médicale (INSERM) U1147, Saints-Pères Research Center Paris, France; Paris Descartes University Paris, France; Clinical Chemistry and.
authors.forename: Pierre
authors.initials: P
authors.lastname: Laurent-Puig
authors.affiliation: Molecular Oncology Research Institute, Tufts Medical Center, Boston, Massachusetts;
authors.forename: Shuping
authors.initials: S
authors.lastname: Li
authors.affiliation: Paris Cardiovascular Research Centre, INSERM, Paris, France; and.
authors.forename: Pierre-Louis
authors.initials: PL
authors.lastname: Tharaux
authors.affiliation: Institut National de la Sante et de la Recherche Médicale (INSERM) U1147, Saints-Pères Research Center Paris, France; Paris Descartes University Paris, France; Clinical Chemistry and.
authors.forename: Philippe
authors.initials: P
authors.lastname: Beaune
authors.affiliation: Paris Descartes University Paris, France; Nephrology Departments, Georges Pompidou European Hospital Paris, France;
authors.forename: Eric
authors.initials: E
authors.lastname: Thervet
authors.affiliation: INSERM, UMR-U1053, Team Endoplasmic Reticulum Stress and Cancer, Bordeaux, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Chevet
authors.affiliation: Molecular Oncology Research Institute, Tufts Medical Center, Boston, Massachusetts;
authors.forename: Guo-Fu
authors.initials: GF
authors.lastname: Hu
authors.affiliation: Institut National de la Sante et de la Recherche Médicale (INSERM) U1147, Saints-Pères Research Center Paris, France; Paris Descartes University Paris, France; Clinical Chemistry and Nephrology Departments, Georges Pompidou European Hospital Paris, France; npallet@yahoo.fr.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Pallet
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D000222:Adaptation, Physiological; D000818:Animals; D017209:Apoptosis; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism; D059865:Endoplasmic Reticulum Stress / Q000502:physiology*; D004722:Endoribonucleases / Q000235:genetics / Q000378:metabolism; D004847:Epithelial Cells; D020868:Gene Silencing; D006801:Humans; D007668:Kidney / Q000473:pathology* / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D014176:Protein Biosynthesis / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D000071701:Regulatory Factor X Transcription Factors; D012259:Ribonuclease, Pancreatic / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D014415:Tunicamycin; D000071717:X-Box Binding Protein 1
chemical_list: D004268:DNA-Binding Proteins; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors; D000071717:X-Box Binding Protein 1; C000605543:XBP1 protein, human; C000605544:Xbp1 protein, mouse; C000605545:Xbp1 protein, rat; D014415:Tunicamycin; D011065:Poly(ADP-ribose) Polymerases; C528229:ERN1 protein, human; D017346:Protein Serine-Threonine Kinases; D004722:Endoribonucleases; C046366:angiogenin; D012259:Ribonuclease, Pancreatic
keywords: acute renal failure; apoptosis; cell biology and structure; chronic allograft nephropathy; renal cell biology; renal epithelial cell