A specific phosphorylation regulates the protective role of αA-crystallin in diabetes

Ruebsam, Anne; Dulle, Jennifer E.; Myers, Angela M; Sakrikar, Dhananjay; Green, Katelyn M.; Khan, Naheed W.; Schey, Kevin L.; Fort, Patrice E.

doi:10.1172/jci.insight.97919

Cited by 39 publications

(83 citation statements)

References 47 publications

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“…28,[32][33][34] Their expression is dramatically upregulated in numerous retinal diseases, such as mechanical injury, ischemic insults, age-related macular degeneration (AMD), uveoretinitis, and DR. 28 Concerning the potential therapeutic value of crystallins in retinal diseases, their exact functions are emerging. 27,35 Namely, the recently discovered roles for aBcrystallin in mediating TGF-b induced epithelial-mesenchymal transformation (EMT) and subretinal fibrosis in AMD, 27 while aA-crystallin providing neuroprotection for retina in DR, 35 point out the opposite therapeutic values for these crystallinfamily members. 27,36 A large number of proteins was also downregulated in response to hypoxia in retina.…”

Section: Discussionmentioning

confidence: 99%

SWATH-MS Proteomic Analysis of Oxygen-Induced Retinopathy Reveals Novel Potential Therapeutic Targets

Vähätupa

Nättinen

Jylhä

et al. 2018

Invest. Ophthalmol. Vis. Sci.

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Section: Discussionmentioning

confidence: 99%

SWATH-MS Proteomic Analysis of Oxygen-Induced Retinopathy Reveals Novel Potential Therapeutic Targets

Vähätupa

Nättinen

Jylhä

et al. 2018

Invest. Ophthalmol. Vis. Sci.

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“…Recent studies revealed that α-crystallins are rapidly upregulated in models of acute retinal injury, including light toxicity and trauma, suggesting that α-crystallins play a role in the retina’s response to cellular stress and damage [ 195 , 196 , 197 ]. We recently demonstrated that these chaperones were highly expressed in both RGCs and Müller glial cells of diabetic animals and human patients with DR [ 198 ]. Of note, αA-crystallins not only inhibit pro-apoptotic pathways in retinal neurons, but also act as a secreted pro-survival factor [ 198 ] and modulator of the expression of inflammatory molecules by glial cells (unpublished data), for the first time establishing a direct link between α-crystallins and neuro-inflammation.…”

Section: Emerging Trends In Inflammation-related Mediators Of Diabmentioning

confidence: 99%

“…We recently demonstrated that these chaperones were highly expressed in both RGCs and Müller glial cells of diabetic animals and human patients with DR [ 198 ]. Of note, αA-crystallins not only inhibit pro-apoptotic pathways in retinal neurons, but also act as a secreted pro-survival factor [ 198 ] and modulator of the expression of inflammatory molecules by glial cells (unpublished data), for the first time establishing a direct link between α-crystallins and neuro-inflammation. Consistent with a critical role in glial cells, α-crystallins have been reported to be upregulated in astrocytes of patients with Alexander disease and microglial cells of patients with Alzheimer’s disease [ 199 , 200 , 201 ].…”

Section: Emerging Trends In Inflammation-related Mediators Of Diabmentioning

confidence: 99%

Role of Inflammation in Diabetic Retinopathy

Rübsam

Parikh

Fort

2018

IJMS

583

471

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Diabetic retinopathy is a common complication of diabetes and remains the leading cause of blindness among the working-age population. For decades, diabetic retinopathy was considered only a microvascular complication, but the retinal microvasculature is intimately associated with and governed by neurons and glia, which are affected even prior to clinically detectable vascular lesions. While progress has been made to improve the vascular alterations, there is still no treatment to counteract the early neuro-glial perturbations in diabetic retinopathy. Diabetes is a complex metabolic disorder, characterized by chronic hyperglycemia along with dyslipidemia, hypoinsulinemia and hypertension. Increasing evidence points to inflammation as one key player in diabetes-associated retinal perturbations, however, the exact underlying molecular mechanisms are not yet fully understood. Interlinked molecular pathways, such as oxidative stress, formation of advanced glycation end-products and increased expression of vascular endothelial growth factor have received a lot of attention as they all contribute to the inflammatory response. In the current review, we focus on the involvement of inflammation in the pathophysiology of diabetic retinopathy with special emphasis on the functional relationships between glial cells and neurons. Finally, we summarize recent advances using novel targets to inhibit inflammation in diabetic retinopathy.

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“…Although there is limited research on the role of Hsps in differentiating glia, Hsps are expressed and induced in mature glia ( Krueger et al, 1999 ; Dean and Tytell, 2001 ; Kalesnykas et al, 2008 ), and our group and others have recently suggested that Hsps play an important role in these cells ( Ruebsam et al, 2018 ). In addition to their critical house-keeping functions and pro-survival role in mature cells under stress, Hsps also exhibit specific patterns of expression during glial development.…”

Section: Heat Shock Proteins Potential Role In Neuronal and Glial Difmentioning

confidence: 99%

Heat Shock Proteins Regulatory Role in Neurodevelopment

2018

Self Cite

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Heat shock proteins (Hsps) are a large family of molecular chaperones that are well-known for their roles in protein maturation, re-folding and degradation. While some Hsps are constitutively expressed in certain regions, others are rapidly upregulated in the presence of stressful stimuli. Numerous stressors, including hyperthermia and hypoxia, can induce the expression of Hsps, which, in turn, interact with client proteins and co-chaperones to regulate cell growth and survival. Such interactions must be tightly regulated, especially at critical points during embryonic and postnatal development. Hsps exhibit specific patterns of expression consistent with a spatio-temporally regulated role in neurodevelopment. There is also growing evidence that Hsps may promote or inhibit neurodevelopment through specific pathways regulating cell differentiation, neurite outgrowth, cell migration, or angiogenesis. This review will examine the regulatory role that these individual chaperones may play in neurodevelopment, and will focus specifically on the signaling pathways involved in the maturation of neuronal and glial cells as well as the underlying vascular network.

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A specific phosphorylation regulates the protective role of αA-crystallin in diabetes

Cited by 39 publications

References 47 publications

SWATH-MS Proteomic Analysis of Oxygen-Induced Retinopathy Reveals Novel Potential Therapeutic Targets

SWATH-MS Proteomic Analysis of Oxygen-Induced Retinopathy Reveals Novel Potential Therapeutic Targets

Role of Inflammation in Diabetic Retinopathy

Heat Shock Proteins Regulatory Role in Neurodevelopment

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