title: Crosstalk between the unfolded protein response and NF-κB-mediated inflammation in the progression of chronic kidney disease.
abstract: The chronic inflammatory response is emerging as an important therapeutic target in progressive chronic kidney disease. A key transcription factor in the induction of chronic inflammation is NF-κB. Recent studies have demonstrated that sustained activation of the unfolded protein response (UPR) can initiate this NF-κB signaling phenomenon and thereby induce chronic kidney disease progression. A key factor influencing chronic kidney disease progression is proteinuria and this condition has now been demonstrated to induce sustained UPR activation. This review details the crosstalk between the UPR and NF-κB pathways as pertinent to chronic kidney disease. We present potential tools to study this phenomenon as well as potential therapeutics that are emerging to regulate the UPR. These therapeutics may prevent inflammation specifically induced in the kidney due to proteinuria-induced sustained UPR activation.
authors.affiliation: Department of Medicine, Division of Nephrology, McMaster University and St. Joseph's Healthcare Hamilton, 50 Charlton Avenue East, Hamilton, ON, Canada L8N 4A6.
authors.forename: Zahraa
authors.identifier: 0000-0001-8436-0553
authors.initials: Z
authors.lastname: Mohammed-Ali
authors.affiliation: Department of Medicine, Division of Nephrology, McMaster University and St. Joseph's Healthcare Hamilton, 50 Charlton Avenue East, Hamilton, ON, Canada L8N 4A6.
authors.forename: Gaile L
authors.initials: GL
authors.lastname: Cruz
authors.affiliation: Department of Medicine, Division of Nephrology, McMaster University and St. Joseph's Healthcare Hamilton, 50 Charlton Avenue East, Hamilton, ON, Canada L8N 4A6.
authors.forename: Jeffrey G
authors.initials: JG
authors.lastname: Dickhout
mesh_terms: D002082:Butylamines / Q000494:pharmacology; D002934:Cinnamates / Q000494:pharmacology; D018450:Disease Progression; D059865:Endoplasmic Reticulum Stress / Q000502:physiology*; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000473:pathology*; D018836:Inflammation Mediators / Q000378:metabolism; D016328:NF-kappa B / Q000276:immunology; D011507:Proteinuria / Q000473:pathology*; D051436:Renal Insufficiency, Chronic / Q000473:pathology*; D015398:Signal Transduction / Q000276:immunology; D013449:Sulfonamides / Q000494:pharmacology; D013450:Sulfones / Q000494:pharmacology; D013876:Thiophenes / Q000494:pharmacology; D013890:Thiourea / Q000031:analogs & derivatives / Q000494:pharmacology; D056811:Unfolded Protein Response / Q000187:drug effects / Q000502:physiology*
chemical_list: C121358:4-phenylbutylamine; D002082:Butylamines; D002934:Cinnamates; D018836:Inflammation Mediators; D016328:NF-kappa B; C556690:STF 083010; D013449:Sulfonamides; D013450:Sulfones; D013876:Thiophenes; C496827:salubrinal; C002010:4-(2-aminoethyl)benzenesulfonylfluoride; D013890:Thiourea