Abstract
Heat shock protein 27 (HSP27) is one of the small molecular chaperones and is involved in many cell mechanisms. Besides the known protective and helpful functions of intracellular HSP27, very little is known about the mode of action of extracellular HSP27. In a previous study, we showed that intravitreal injection of HSP27 led to neuronal damage in the retina and optic nerve after 21 days. However, it was not clear which degenerative signaling pathways were induced by the injection. For this reason, the pathological mechanisms of intravitreal HSP27 injection after 14 days were investigated. Histological and RT-qPCR analyses revealed an increase in endogenous HSP27 in the retina and an activation of components of the intrinsic and extrinsic apoptosis pathway. In addition, an increase in nucleus factor-kappa-light-chain-enhancer of activated B cells (NFκB), as well as of microglia/macrophages and T-cells could be observed. In the optic nerve, however, only an increased apoptosis rate was detectable. Therefore, the activation of caspases and the induction of an incipient immune response seem to be the main triggers for retinal degeneration in this intravitreal HSP27 model.
Highlights
Heat shock proteins (HSPs) are molecular chaperones, and they are upregulated in response to physiological and environmental stressors [1]
According to these overview stains, we noted that HSP25 was mainly located in the ganglion cell layer (GCL)
We demonstrated that extracellular Heat shock protein 27 (HSP27) induced degenerative signaling pathways, including caspase activation, leading to cell death
Summary
Heat shock proteins (HSPs) are molecular chaperones, and they are upregulated in response to physiological and environmental stressors [1]. HSPs can be classified into different groups according to their molecular weight [2] Larger proteins, such as HSP70 and HSP60 chaperones, are found in the cytosol, endoplasmic reticulum, mitochondria, and the cell nucleus, as well as in the extracellular environment [3,4]. One of the smaller HSPs is HSP27, known as HSP25 or heat shock protein beta-1 (HspB1) It is ubiquitously expressed and is involved in various biological functions [5]. Increased anti-inflammatory factors, such as IL-10 and GM-CSF, were detected at both mRNA and protein levels [9]. This suggests that the mode of action of HSP27 may depend on the localization
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