2008 JASN IMPACT FACTOR 7.505	HOME   AUTHOR INFO   EDITORIAL BOARD   SUBSCRIBE   FEEDBACK   ALERTS   HELP
advanced	CURRENT ISSUE	ARCHIVES	JASN Express	ONLINE SUBMISSION

This Article Full Text (Rapid PDF) Supplemental Data Files All Versions of this Article: ASN.2007040469v1 19/3/547    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Grigoryev, D. N. Articles by Rabb, H. Search for Related Content PubMed PubMed Citation Articles by Grigoryev, D. N. Articles by Rabb, H.

Received April 17, 2007
Accepted on October 17, 2007

BASIC RESEARCH

The Local and Systemic Inflammatory Transcriptome after Acute Kidney Injury

Dmitry N. Grigoryev ^*1, Manchang Liu ^*, Heitham T. Hassoun , Chris Cheadle ^*, Kathleen C. Barnes ^*, and Hamid Rabb ^*

*Departments of Medicine and Surgery, Johns Hopkins University, Baltimore, Maryland

¹ To whom correspondence should be addressed. E-mail: dgrigor1{at}jhmi.edu.

	Abstract

Studies in humans and animal models have demonstrated that acute kidney injury (AKI) has a significant effect on the function of extrarenal organs. The combination of AKI and lung dysfunction is associated with 80% mortality; the lung, because of its extensive capillary network, is a prime target for AKI-induced effects. The study presented here tested the hypothesis that AKI leads to a vigorous inflammatory response and produces distinct genomic signatures in the kidney and lung. In a murine model of ischemic AKI, prominent global transcriptomic changes and histologic injury in both kidney and lung tissues were identified. These changes were evident at both early (6 h) and late (36 h) timepoints after 60-min bilateral kidney ischemia and were more prominent than similar timepoints after sham surgery or 30 min of ischemia. The inflammatory transcriptome (109 genes) of both organs changed with marked similarity, including the innate immunity genes Cd14, Socs3, Saa3, Lcn2, and Il1r2. Functional genomic analysis of these genes suggested that IL-10 and IL-6 signaling was involved in the distant effects of local inflammation, and this was supported by increased serum levels of IL-10 and IL-6 after ischemia-reperfusion. In summary, this is the first comprehensive analysis of concomitant inflammation-associated transcriptional changes in the kidney and a remote organ during AKI. Functional genomic analysis identified potential mediators that connect local and systemic inflammation, suggesting that this type of analysis may be a useful discovery tool for novel biomarkers and therapeutic drug development.

This article has been cited by other articles:

				J. Floege and S. Uhlig Kidney calling lung and call back: how organs talk to each other Nephrol. Dial. Transplant., September 15, 2009; (2009) gfp464v1. [Full Text] [PDF]

				M. Naito, R. A. Zager, and K. Bomsztyk BRG1 Increases Transcription of Proinflammatory Genes in Renal Ischemia J. Am. Soc. Nephrol., August 1, 2009; 20(8): 1787 - 1796. [Abstract] [Full Text] [PDF]

				H. T. Hassoun, M. L. Lie, D. N. Grigoryev, M. Liu, R. M. Tuder, and H. Rabb Kidney ischemia-reperfusion injury induces caspase-dependent pulmonary apoptosis Am J Physiol Renal Physiol, July 1, 2009; 297(1): F125 - F137. [Abstract] [Full Text] [PDF]

				K. J. Kelly, B. Kluve-Beckerman, and J. H. Dominguez Acute-phase response protein serum amyloid A stimulates renal tubule formation: studies in vitro and in vivo Am J Physiol Renal Physiol, June 1, 2009; 296(6): F1355 - F1363. [Abstract] [Full Text] [PDF]

				C. E. Hobson, S. Yavas, M. S. Segal, J. D. Schold, C. G. Tribble, A. J. Layon, and A. Bihorac Acute Kidney Injury Is Associated With Increased Long-Term Mortality After Cardiothoracic Surgery Circulation, May 12, 2009; 119(18): 2444 - 2453. [Abstract] [Full Text] [PDF]

				V. A. Luyckx, L. V. Cairo, C. A. Compston, W. L. Phan, and T. F. Mueller Oncostatin M pathway plays a major role in the renal acute phase response Am J Physiol Renal Physiol, April 1, 2009; 296(4): F875 - F883. [Abstract] [Full Text] [PDF]

				J. M. Dodd-o, M. Hristopoulos, D. Scharfstein, R. Brower, P. Hassoun, L. S. King, P. Becker, M. Liu, W. Wang, H. T. Hassoun, et al. Interactive effects of mechanical ventilation and kidney health on lung function in an in vivo mouse model Am J Physiol Lung Cell Mol Physiol, January 1, 2009; 296(1): L3 - L11. [Abstract] [Full Text] [PDF]

				P. Devarajan Neutrophil gelatinase-associated lipocalin--an emerging troponin for kidney injury Nephrol. Dial. Transplant., December 1, 2008; 23(12): 3737 - 3743. [Full Text] [PDF]

				M. Liu, Y. Liang, S. Chigurupati, J. D. Lathia, M. Pletnikov, Z. Sun, M. Crow, C. A. Ross, M. P. Mattson, and H. Rabb Acute Kidney Injury Leads to Inflammation and Functional Changes in the Brain J. Am. Soc. Nephrol., July 1, 2008; 19(7): 1360 - 1370. [Abstract] [Full Text] [PDF]

Copyright © 2009 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673