A protective role of unfolded protein response in mouse ischemic acute kidney injury

• Published in: European journal of pharmacology Vol. 592; no. 1; pp. 138 - 145
• Main Authors: Prachasilchai, Worapat, Sonoda, Hiroko, Yokota-Ikeda, Naoko, Oshikawa, Sayaka, Aikawa, Chie, Uchida, Kazuyuki, Ito, Katsuaki, Kudo, Takashi, Imaizumi, Kazunori, Ikeda, Masahiro
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 11.09.2008; Elsevier
• Subjects: Animals; Biological and medical sciences; Blotting, Western; Cardiology. Vascular system; DNA-Binding Proteins - biosynthesis; DNA-Binding Proteins - genetics; Endoplasmic reticulum stress; Enzyme Inhibitors - pharmacology; Glucose-regulated protein 78; Heat-Shock Proteins - biosynthesis; Heat-Shock Proteins - genetics; Ischemia-reperfusion injury; Kidney - pathology; Kidney Diseases - drug therapy; Kidney Diseases - pathology; Kidney Function Tests; Kidneys; Male; Medical sciences; Mice; Molecular Chaperones - biosynthesis; Molecular Chaperones - genetics; Nephrology. Urinary tract diseases; Pharmacology. Drug treatments; Protein Folding; Regulatory Factor X Transcription Factors; Renal Circulation - physiology; Reperfusion Injury - drug therapy; Reperfusion Injury - pathology; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - biosynthesis; RNA, Messenger - genetics; Thapsigargin; Thapsigargin - pharmacology; Transcription Factors - biosynthesis; Transcription Factors - genetics; Tunicamycin; Tunicamycin - pharmacology; Unfolded protein response; Urinary system involvement in other diseases. Miscellaneous; X-box binding protein; X-Box Binding Protein 1; Thapsigargin; Ischemia-reperfusion injury; Glucose-regulated protein 78; Tunicamycin; X-box binding protein; Endoplasmic reticulum stress; Unfolded protein response; Kidney disease; Antineoplastic agent; Urinary system disease; Ischemia reperfusion; Acute kidney injury; Rodentia; Lactone; Glucose; Stress; Prevention; Binding protein; Vertebrata; Mammalia; Mouse; Sesquiterpenes; Animal; Endoplasmic reticulum
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2008.06.108

Although renal ischemia-reperfusion is known to activate the unfolded protein response, the renal site and role of activation of this response following the insult in vivo remains largely unknown. Here we studied the renal spatio-temporal expression pattern of glucose-regulated protein (GRP) 78, a central regulator of the unfolded protein response network, following renal ischemia-reperfusion and the effects of the specific chemical unfolded protein response inducers, tunicamycin and thapsigargin, on renal ischemia-reperfusion injury in mice. Renal ischemia-reperfusion resulted in expression of the spliced form of the X-box binding protein-1 (XBP-1s) transcript, an unfolded protein response target, at 1 and 2 h after the insult. This response was followed by an increase in the GRP78 transcript and protein. The increased amount of GRP78 protein after ischemia-reperfusion was largely localized in proximal tubule cells. Pretreatment with tunicamycin or thapsigargin significantly ameliorated renal dysfunction and injury after ischemia-reperfusion. Taken together with these results, the unfolded protein response was activated following renal ischemia-reperfusion at sites that are susceptible to ischemia-reperfusion injury, and this activation had a protective effect against renal ischemia-reperfusion injury in vivo. Molecules involved in the unfolded protein response may offer new opportunities for pharmacological intervention against renal ischemia-reperfusion injury, which is an important cause of acute kidney injury.