scholarly journals Mice that overexpress human heat shock protein 27 have increased renal injury following ischemia reperfusion

2009 ◽  
Vol 75 (5) ◽  
pp. 499-510 ◽  
Author(s):  
Sean W.C. Chen ◽  
Minjae Kim ◽  
Mihwa Kim ◽  
Joseph H. Song ◽  
Sang Won Park ◽  
...  
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Renal Injury ◽  
Ischemia Reperfusion ◽  
Heat Shock Protein 27 ◽  
Human Heat Shock Protein

scholarly journals Selective renal overexpression of human heat shock protein 27 reduces renal ischemia-reperfusion injury in mice

2010 ◽  
Vol 299 (2) ◽  
pp. F347-F358 ◽  
Author(s):  
Minjae Kim ◽  
Sang Won Park ◽  
Mihwa Kim ◽  
Sean W. C. Chen ◽  
William T. Gerthoffer ◽  
...  
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Fluorescent Protein ◽  
Ischemia Reperfusion Injury ◽  
Therapeutic Option ◽  
Ischemia Reperfusion ◽  
Heat Shock Protein 27 ◽  
Renal Ischemia ◽  
Specific Expression ◽  
Mrna Induction

We have previously shown that exogenous and endogenous A1 adenosine receptor (A1AR) activation protected against renal ischemia-reperfusion (IR) injury in mice by induction and phosphorylation of heat shock protein 27 (HSP27). With global overexpression of HSP27 in mice, however, there was a paradoxical increase in systemic inflammation with increased renal injury after an ischemic insult due to increased NK1.1 cytotoxicity. In this study, we hypothesized that selective renal expression of HSP27 in mice would improve renal function and reduce injury after IR. Mice were subjected to renal IR injury 2 days after intrarenal injection of saline or a lentiviral construct encoding enhanced green fluorescent protein (EGFP) or human HSP27 coexpressing EGFP (EGFP-huHSP27). Mice with kidney-specific reconstitution of huHSP27 had significantly lower plasma creatinine, renal necrosis, apoptosis, and inflammation as demonstrated by decreased proinflammatory cytokine mRNA induction and neutrophil infiltration. In addition, there was better preservation of the proximal tubule epithelial filamentous (F)-actin cytoskeleton in the huHSP27-reconstituted groups than in the control groups. Furthermore, huHSP27 overexpression led to increased colocalization with F-actin in renal proximal tubules. Taken together, these findings have important clinical implications, as they imply that kidney-specific expression of HSP27 through lentiviral delivery is a viable therapeutic option in attenuating the effects of renal IR.

scholarly journals Human Heat Shock Protein 27 Overexpressing Mice Are Protected Against Hepatic Ischemia and Reperfusion Injury

2009 ◽  
Vol 87 (10) ◽  
pp. 1478-1487 ◽  
Author(s):  
Sean W.C. Chen ◽  
Sang Won Park ◽  
Mihwa Kim ◽  
Kevin M. Brown ◽  
Vivette D. D’Agati ◽  
...  
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Reperfusion Injury ◽  
Heat Shock Protein 27 ◽  
Ischemia And Reperfusion ◽  
Ischemia And Reperfusion Injury ◽  
Hepatic Ischemia ◽  
Human Heat Shock Protein

Abstract 49: Endothelial-targeted Overexpression of Heat Shock Protein 27 Ameliorates Rapid Blood Brain Barrier Impairment and Improves Long Term Outcomes After Ischemia and Reperfusion

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Yejie Shi ◽  
Xiaoyan Jiang ◽  
Lili Zhang ◽  
Hongjian Pu ◽  
Wenting Zhang ◽  
...  
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Blood Brain Barrier ◽  
Actin Polymerization ◽  
Ischemia Reperfusion ◽  
Neurovascular Unit ◽  
Heat Shock Protein 27 ◽  
Fiber Formation ◽  
Brain Barrier ◽  
Blood Brain

Introduction: Blood brain barrier (BBB) damage resulting from ischemia/reperfusion (I/R) disrupts the neurovascular unit and leads to poor patient outcomes. We recently discovered that caveolin-1-independent subtle structural aberrations of brain microvascular endothelial cells (BMECs), such as abnormal actin polymerization, stress fiber formation and subsequent junctional protein (JP) disassembly, are a novel mechanism for rapid BBB breach after I/R. Hypothesis: Heat shock protein 27 (HSP27) reduces BBB breakdown after I/R by inhibiting actin polymerization and JP disassembly in BMECs. Methods: Neuron- or EC-specific HSP27-overexpressing mice were subjected to 1 h MCAO and reperfusion. BBB damage, tissue histology, and neurobehavioral performance were assessed up to 35 d after I/R. I/R-induced BBB damage was also simulated in BMEC cultures, where gene manipulations were achieved using lentiviral vectors. Cell-permeable TAT-HSP27 protein was injected i.v. into mice after I/R to rapidly elevate HSP27 in BMECs. Results: Targeted overexpression of HSP27 within ECs—but not neurons—was sufficient to reduce early (1-3 h) and late (24 h) BBB damage after I/R (p<0.01). Mechanistically, HSP27 suppressed I/R-induced actin polymerization, stress fibers, and JP disassembly in BMECs, but independent of its anti-cell death properties. Intracerebral infiltration of neutrophils and macrophages was attenuated in EC-HSP27 mice by 35% and 60%, respectively (n=6, p<0.05) at 48 h after I/R. Infarct size was reduced by 35% at 72 h, and sensorimotor functions (p<0.01, cylinder and corner tests) were improved in EC-HSP27 mice up to 21 d. Post-I/R injection of TAT-HSP27 markedly reduced BBB damage and elicited sustained (up to 35 d) protection against neurological deficits. Conclusions: HSP27 protects against BBB disruption after I/R by inhibiting actin polymerization and JP disassembly in BMECs. HSP27 may be a therapy for ischemic stroke in conjunction with reperfusion.

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