Heat Shock Protein 27 Protects Lung Epithelial Cells From Hyperoxia-Induced Apoptotic Cell Death

Shao, Lei; Perez, Ricardo E.; Gerthoffer, William T.; Truog, William E.; Xu, Da-Zhong

doi:10.1203/pdr.0b013e3181961a51

Cited by 12 publications

(8 citation statements)

References 44 publications

(37 reference statements)

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“…HSP27 can also inhibit apoptosis and stabilize the actin cytoskeleton, leading to increased resistance against cell death. HSP27 overexpression has been shown to be protective in the brain, liver, lung and heart (5,29,38,41). HSP27 can be phosphorylated or upregulated to protect the cell against stress or injury (6) and has also been shown to translocate to the nucleus to interact with transcription factors and stimulate gene transcription (9).…”

Section: Discussionmentioning

confidence: 99%

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

Kim¹,

Park²,

Kim³

et al. 2010

American Journal of Physiology-Renal Physiology

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We have previously shown that exogenous and endogenous A(1) adenosine receptor (A(1)AR) 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.

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Section: Discussionmentioning

confidence: 99%

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

Kim¹,

Park²,

Kim³

et al. 2010

American Journal of Physiology-Renal Physiology

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“…It has not been established in the bleomycin model whether Hsp70 is signalling through TLRs or other receptors, and whether the protection observed might be attributable to direct TLR‐dependent pro‐survival effects on the respiratory epithelium. Conversely, Hsp27 expression was decreased in respiratory epithelial cells after exposure to 95% FiO2 and was linked with less hyperoxia‐induced apoptosis when compared to controls, implying that there are disparate effects of the various HSPs .…”

Section: Stress Response Moleculesmentioning

confidence: 96%

Danger‐associated molecular patterns (DAMPs) in acute lung injury

Tolle

Standiford

2012

The Journal of Pathology

133

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Danger-associated molecular patterns (DAMPs) are host-derived molecules that can function to regulate the activation of pathogen recognition receptors (PRRs). These molecules play a critical role in modulating the lung injury response. DAMPs originate from multiple sources, including injured and dying cells, the extracellular matrix, or exist as immunomodulatory proteins within the airspace and interstitium. DAMPs can function as either toll-like receptor (TLR) agonists or antagonists, and can modulate both TLR and nod-like receptor (NLR) signalling cascades. Collectively, this diverse group of molecules may represent important therapeutic targets in the prevention and/or treatment of acute lung injury (ALI) and its more severe form, acute respiratory distress syndrome (ARDS).

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“…Hyperoxia exposure upregulates the expression of CTGF, and therefore administration of a CTGF-neutralizing antibody was able to protect alveolarization and vascular development, as well as pulmonary hypertension in the rat BPD model (2). More recently other experimental techniques in the rat BPD model, such as the use of siRNA to inhibit expression of important lung development factors, have helped identify possible targets for lung repair in BPD (51,60,70).…”

Section: L954mentioning

confidence: 99%

Animal models of bronchopulmonary dysplasia. The term rat models

O’Reilly

Thébaud

2014

American Journal of Physiology-Lung Cellular and Molecular Phys

177

149

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O'Reilly M, Thébaud B. Animal models of bronchopulmonary dysplasia. The term rat models. Am J Physiol Lung Cell Mol Physiol 307: L948 -L958, 2014. First published October 10, 2014; doi:10.1152/ajplung.00160.2014.-Bronchopulmonary dysplasia (BPD) is the chronic lung disease of prematurity that affects very preterm infants. Although advances in perinatal care have enabled the survival of infants born as early as 23-24 wk of gestation, the challenge of promoting lung growth while protecting the ever more immature lung from injury is now bigger. Consequently, BPD remains one of the most common complications of extreme prematurity and still lacks specific treatments. Progress in our understanding of BPD and the potential of developing therapeutic strategies have arisen from large (baboons, sheep, and pigs) and small (rabbits, rats, and mice) animal models. This review focuses specifically on the use of the rat to model BPD and summarizes how the model is used in various research studies and the advantages and limitations of this particular model, and it highlights recent therapeutic advances in BPD by using this rat model. hyperoxia; lung development; premature birth BRONCHOPULMONARY DYSPLASIA (BPD) is the most common chronic lung disease of very preterm infants. BPD interrupts lung development and has serious long-term respiratory complications that reach beyond childhood and into adult life (8,25,26,41,53). The multifactorial etiology of BPD has prompted research to investigate the many factors contributing to the pathogenesis of BPD (reviewed in Ref. 38), with the ultimate aim of developing effective therapies to prevent longterm pulmonary sequelae. To investigate the effectiveness of various therapeutic strategies on the development, structure, and function of the lungs, it is important to have animal models that reliably reproduce some of the features observed in very preterm infants developing BPD. To achieve this, known contributing factors of BPD, such as perinatal inflammation, growth restriction, hyperoxia, and mechanical ventilation, have been used in both large and small animals to mimic the BPD-like lung injury. In particular, exposure of neonatal rats to hyperoxia is extensively utilized as a small animal model of experimental BPD. Characterization of the Rat Model of Experimental BPDExposing the immature rat lung to hyperoxic gas through neonatal life closely reproduces the histopathology observed in human infants with BPD. Studies have shown that exposure of the developing rat lung to hyperoxic gas can have detrimental effects, particularly on the structure of the gas-exchanging region (14,30,34,46,62,66). The main overall finding, which is common to each study, is that exposure of the immature lung to hyperoxic gas impairs alveolarization, resulting in fewer and enlarged alveolar air spaces. Pulmonary hypertension, disrupted vascular growth, vascular leakage, accumulation of plasma proteins, extravascular fibrin deposition, increased lung collagen content, increased inflammatory cell influx, and diso...

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Heat Shock Protein 27 Protects Lung Epithelial Cells From Hyperoxia-Induced Apoptotic Cell Death

Cited by 12 publications

References 44 publications

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

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

Danger‐associated molecular patterns (DAMPs) in acute lung injury

Animal models of bronchopulmonary dysplasia. The term rat models

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