Transcriptional analysis of infiltrating T cells in kidney ischemia-reperfusion injury reveals a pathophysiological role for CCR5
- Authors
- Ko, Gang Jee; Linfert, Douglas; Jang, Hye Ryoun; Higbee, Elizabeth; Watkins, Tonya; Cheadle, Chris; Liu, Manchang; Racusen, Lorraine; Grigoryev, Dmitry N.; Rabb, Hamid
- Issue Date
- Mar-2012
- Publisher
- AMER PHYSIOLOGICAL SOC
- Keywords
- acute kidney injury; T lymphocyte; array-based QRT-PCR; chemokine receptor 5
- Citation
- AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY, v.302, no.6, pp.F762 - F773
- Indexed
- SCIE
SCOPUS
- Journal Title
- AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
- Volume
- 302
- Number
- 6
- Start Page
- F762
- End Page
- F773
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/105346
- DOI
- 10.1152/ajprenal.00335.2011
- ISSN
- 1931-857X
- Abstract
- Ko GJ, Linfert D, Jang HR, Higbee E, Watkins T, Cheadle C, Liu M, Racusen L, Grigoryev DN, Rabb H. Transcriptional analysis of infiltrating T cells in kidney ischemia-reperfusion injury reveals a pathophysiological role for CCR5. Am J Physiol Renal Physiol 302: F762-F773, 2012. First published December 7, 2011; doi:10.1152/ajprenal.00335.2011.-Although T cells have been shown to play a direct role in kidney ischemia-reperfusion injury (IRI), little is known about the underlying mechanisms. We hypothesized that studying the transcriptional responses in kidney-infiltrating T cells would help elucidate novel therapeutic targets for kidney IRI. Unilateral renal pedicle clamping for 45 min was performed in male C57BL/6 mice, and CD3(+) T cells were isolated from the kidney and purified. Transcriptional activities of T cell were measured by array-based PCR compared between ischemic kidneys and contralateral nonischemic kidneys. Among total of 89 genes analyzed, 24, 22, 24, and 37 genes were significantly changed at 6 h, day 3, day 10, and day 28 after IRI. Genes associated with cytokines, chemokines, and costimulatory molecules were upregulated. Pathway analysis identified CC motif chemokine receptor 5 (CCR5) as a candidate pathophysiological pathway. CCR5 upregulation was validated at the protein level, and CCR5 blockade improved renal function after kidney IRI. Using discovery techniques to identify transcriptional responses in purified kidney-infiltrating cells enabled the elucidation of novel mechanisms and therapeutic targets for IRI.
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