title: Calcium Oxalate Induces Renal Injury through Calcium-Sensing Receptor.
abstract: Objective.To investigate whether calcium-sensing receptor (CaSR) plays a role in calcium-oxalate-induced renal injury.Materials and Methods.HK-2 cells and rats were treated with calcium oxalate (CaOx) crystals with or without pretreatment with the CaSR-specific agonist gadolinium chloride (GdCl3) or the CaSR-specific antagonist NPS2390. Changes in oxidative stress (OS) in HK-2 cells and rat kidneys were assessed. In addition, CaSR, extracellular signal-regulated protein kinase (ERK), c-Jun N-terminal protein kinase (JNK), and p38 expression was determined. Further, crystal adhesion assay was performedin vitro, and the serum urea and creatinine levels and crystal deposition in the kidneys were also examined.Results.CaOx increased CaSR, ERK, JNK, and p38 protein expression and OSin vitroandin vivo. These deleterious changes were further enhanced upon pretreatment with the CaSR agonist GdCl3but were attenuated by the specific CaSR inhibitor NPS2390 compared with CaOx treatment alone. Pretreatment with GdCl3further increasedin vitroandin vivocrystal adhesion and renal hypofunction. In contrast, pretreatment with NPS2390 decreasedin vitroandin vivocrystal adhesion and renal hypofunction.Conclusions.CaOx-induced renal injury is related to CaSR-mediated OS and increased mitogen-activated protein kinase (MAPK) signaling, which subsequently leads to CaOx crystal adhesion.
authors.affiliation: Department of Urology, Institute of Urology, Gansu Nephro-Urological Clinical Center, Key Laboratory of Urological Diseases in Gansu Province, The Second Hospital of Lanzhou University, Lanzhou, Gansu 730030, China; Department of Urology, The First Affiliated Hospital of Anhui Medical University and Institute of Urology, Anhui Medical University, Hefei, China.
authors.forename: Xiaoran
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Urology, Institute of Urology, Gansu Nephro-Urological Clinical Center, Key Laboratory of Urological Diseases in Gansu Province, The Second Hospital of Lanzhou University, Lanzhou, Gansu 730030, China.
authors.forename: Junhai
authors.initials: J
authors.lastname: Ma
authors.affiliation: Department of Urology, Institute of Urology, Gansu Nephro-Urological Clinical Center, Key Laboratory of Urological Diseases in Gansu Province, The Second Hospital of Lanzhou University, Lanzhou, Gansu 730030, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Shi
authors.affiliation: The First Hospital of Lanzhou University, Lanzhou, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Su
authors.affiliation: Department of Urology, Institute of Urology, Gansu Nephro-Urological Clinical Center, Key Laboratory of Urological Diseases in Gansu Province, The Second Hospital of Lanzhou University, Lanzhou, Gansu 730030, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Fu
authors.affiliation: Department of Urology, Institute of Urology, Gansu Nephro-Urological Clinical Center, Key Laboratory of Urological Diseases in Gansu Province, The Second Hospital of Lanzhou University, Lanzhou, Gansu 730030, China.
authors.forename: Yanlin
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Urology, Institute of Urology, Gansu Nephro-Urological Clinical Center, Key Laboratory of Urological Diseases in Gansu Province, The Second Hospital of Lanzhou University, Lanzhou, Gansu 730030, China.
authors.forename: Jianzhong
authors.initials: J
authors.lastname: Lu
authors.affiliation: Department of Urology, Institute of Urology, Gansu Nephro-Urological Clinical Center, Key Laboratory of Urological Diseases in Gansu Province, The Second Hospital of Lanzhou University, Lanzhou, Gansu 730030, China.
authors.forename: Zhongjin
authors.identifier: 0000-0002-2884-1181
authors.initials: Z
authors.lastname: Yue
mesh_terms: D000218:Adamantane / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D002129:Calcium Oxalate / Q000633:toxicity*; D002460:Cell Line; D003460:Crystallization; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D019855:Ethylene Glycol; D005682:Gadolinium / Q000494:pharmacology; D006801:Humans; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D053040:Nephrolithiasis / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D018384:Oxidative Stress / Q000187:drug effects; D010766:Phosphorylation; D011810:Quinoxalines / Q000494:pharmacology; D017207:Rats, Sprague-Dawley; D044169:Receptors, Calcium-Sensing / Q000187:drug effects* / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: C569355:2-quinoxaline-carboxamide-N-adamantan-1-yl; C095550:CASR protein, human; D011810:Quinoxalines; D044169:Receptors, Calcium-Sensing; C473605:extracellular calcium cation-sensing receptor, rat; D002129:Calcium Oxalate; D005682:Gadolinium; D020928:Mitogen-Activated Protein Kinases; D019855:Ethylene Glycol; C038958:gadolinium chloride; D000218:Adamantane