Heat shock protein expression is highly sensitive to ischemia-reperfusion injury in rat kidneys.
Renal injury is known to trigger upregulation of many intracellular signal proteins, but those most sensitive in responding to renal injury remain debatable. We used gene microarray analysis to compare gene expression in rat kidneys subjected to early ischemia-reperfusion injury (30 min of renal ischemia and 3 hr of reperfusion) with non-ischemic kidneys as controls. Among 31,100 genes analyzed, microarray analysis revealed 21 genes with >3-fold increase in expression in ischemic kidneys compared to control non-ischemic kidneys. These upregulated genes included heat shock protein 70 (43-fold), heat shock protein 27 (12-fold), heme oxygenase-1 (10-fold), kidney injury molecule-1 (8-fold), and several subtypes of S100 calcium-binding proteins (3.1- to 7.5-fold). Following a prolonged reperfusion period (48 hr) after 30 min of ischemia, acute tubular necrosis was obvious in the S3 segment of proximal tubules of ischemic kidneys. Injured proximal tubules showed upregulated expression of heat shock protein 70 by immunohistochemistry and by Western blotting. These data suggest that heat shock proteins (eg, heat shock protein 70, heat shock protein 27, and heme oxygenase-1) are crucial for renal cell response to ischemic injury and that heat shock protein 70 is a highly sensitive intracellular marker of ischemia-reperfusion injury.
Zhang
Ping L
PL
Division of Laboratory Medicine, Geisinger Medical Center, Danville, Pennsylvania, USA. pinglzhang@gmail.com
Lun
Mingyue
M
Schworer
Charles M
CM
Blasick
Thomas M
TM
Masker
Kathryn K
KK
Jones
Jay B
JB
Carey
David J
DJ
D000818:Animals; D015153:Blotting, Western; D016000:Cluster Analysis; D003404:Creatinine / Q000097:blood; D005786:Gene Expression Regulation; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics* / Q000378:metabolism*; D007150:Immunohistochemistry; D007668:Kidney / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000235:genetics* / Q000378:metabolism*; D015854:Up-Regulation
D018840:HSP70 Heat-Shock Proteins; D003404:Creatinine