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Title:
Endoplasmic reticulum stress, the unfolded protein response and autophagy in kidney diseases | Nature Reviews Nephrology
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Our understanding of endoplasmic reticulum (ER) stress, the unfolded protein response (UPR) and ER stress-induced autophagy in the kidney has increased β using the presence of ER chaperones in the urine as a biomarker of renal ER stress, and using pharmacological agents that improve protein folding or induce the expression of chaperones, may aid in the diagnosis and treatment of kidney disease, respectively. Progress has been made in our understanding of the mechanisms of endoplasmic reticulum (ER) proteostasis, ER stress and the unfolded protein response (UPR), as well as ER stress-induced autophagy, in the kidney. Experimental models have revealed that disruption of the UPR, including a protein that senses misfolded proteins (namely, inositol-requiring enzyme 1Ξ±) in mouse podocytes causes podocyte injury and albuminuria as mice age. Protein misfolding and ER stress are evident in various renal diseases, including primary glomerulonephritides, glomerulopathies associated with genetic mutations, diabetic nephropathy, acute kidney injury, chronic kidney disease and renal fibrosis. The induction of ER stress may be cytoprotective, or it may be cytotoxic by activating apoptosis. The UPR may interact in a coordinated manner with autophagy to alleviate protein misfolding and its consequences. Monitoring the excretion of ER chaperones into the urine can potentially serve as a biomarker of renal ER stress. In specific kidney diseases, the treatment of experimental animals with chemical chaperones that improve protein folding or with chaperone inducers has alleviated kidney injury. Given the limited availability of mechanism-based therapies for kidney diseases, normalization of ER stress using pharmacological agents represents a promising therapeutic approach towards preventing or arresting the progression of kidney disease.
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nature portfolio journals nature portfolio permissions reprints privacy policy advertising health research akt/gsk3-beta signaling pathway social media national library research grants author information authors hyperglycemia-induced podocyte injury nature+ nature 454 nature 467 nature set7/9-induced histone methylation inositol-requiring enzyme 1Ξ± inositol-requiring enzyme-1Ξ± dahl salt-sensitive rat complement-mediated glomerular injury n-linked glycosylation sites lead-induced oxidative stress protein-tyrosine phosphatase 1b gov/ct2/show/nct02343094 er stress-induced autophagy albumin overload-induced nephropathy ameliorate protein-folding diseases x-box binding protein-1 personal data ischemia-reperfusion injury attenuates kidney injury erse-ii element hypoxic conditions stimulate endoplasmic reticulum stress endoplasmic-reticulum stress prevent neurodegeneration nf-ΞΊb-mediated inflammation Ξ±-actinin-4-mediated fsgs springerlink instant access data protection acute ischemic injury author correspondence author declares renal tubular injury glomerular basement membrane inhibits cell proliferation acute kidney injury transcription factor xbp-1 impairs cytoskeletal dynamics
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- Stress in the kidney is the road to pERdition: is endoplasmic reticulum stress a pathogenic mediator of diabetic nephropathy?
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Our understanding of endoplasmic reticulum (ER) stress, the unfolded protein response (UPR) and ER stress-induced autophagy in the kidney has increased Γ’ΒΒ using the presence of ER chaperones in the urine as a biomarker of renal ER stress, and using pharmacological agents that improve protein folding or induce the expression of chaperones, may aid in the diagnosis and treatment of kidney disease, respectively. Progress has been made in our understanding of the mechanisms of endoplasmic reticulum (ER) proteostasis, ER stress and the unfolded protein response (UPR), as well as ER stress-induced autophagy, in the kidney. Experimental models have revealed that disruption of the UPR, including a protein that senses misfolded proteins (namely, inositol-requiring enzyme 1ΓΒ±) in mouse podocytes causes podocyte injury and albuminuria as mice age. Protein misfolding and ER stress are evident in various renal diseases, including primary glomerulonephritides, glomerulopathies associated with genetic mutations, diabetic nephropathy, acute kidney injury, chronic kidney disease and renal fibrosis. The induction of ER stress may be cytoprotective, or it may be cytotoxic by activating apoptosis. The UPR may interact in a coordinated manner with autophagy to alleviate protein misfolding and its consequences. Monitoring the excretion of ER chaperones into the urine can potentially serve as a biomarker of renal ER stress. In specific kidney diseases, the treatment of experimental animals with chemical chaperones that improve protein folding or with chaperone inducers has alleviated kidney injury. Given the limited availability of mechanism-based therapies for kidney diseases, normalization of ER stress using pharmacological agents represents a promising therapeutic approach towards preventing or arresting the progression of kidney disease.
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Our understanding of endoplasmic reticulum (ER) stress, the unfolded protein response (UPR) and ER stress-induced autophagy in the kidney has increased Γ’ΒΒ using the presence of ER chaperones in the urine as a biomarker of renal ER stress, and using pharmacological agents that improve protein folding or induce the expression of chaperones, may aid in the diagnosis and treatment of kidney disease, respectively. Progress has been made in our understanding of the mechanisms of endoplasmic reticulum (ER) proteostasis, ER stress and the unfolded protein response (UPR), as well as ER stress-induced autophagy, in the kidney. Experimental models have revealed that disruption of the UPR, including a protein that senses misfolded proteins (namely, inositol-requiring enzyme 1ΓΒ±) in mouse podocytes causes podocyte injury and albuminuria as mice age. Protein misfolding and ER stress are evident in various renal diseases, including primary glomerulonephritides, glomerulopathies associated with genetic mutations, diabetic nephropathy, acute kidney injury, chronic kidney disease and renal fibrosis. The induction of ER stress may be cytoprotective, or it may be cytotoxic by activating apoptosis. The UPR may interact in a coordinated manner with autophagy to alleviate protein misfolding and its consequences. Monitoring the excretion of ER chaperones into the urine can potentially serve as a biomarker of renal ER stress. In specific kidney diseases, the treatment of experimental animals with chemical chaperones that improve protein folding or with chaperone inducers has alleviated kidney injury. Given the limited availability of mechanism-based therapies for kidney diseases, normalization of ER stress using pharmacological agents represents a promising therapeutic approach towards preventing or arresting the progression of kidney disease.
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