Regulation of renal calbindin expression during cisplatin-induced kidney injury.


Journal

Journal of biochemical and molecular toxicology
ISSN: 1099-0461
Titre abrégé: J Biochem Mol Toxicol
Pays: United States
ID NLM: 9717231

Informations de publication

Date de publication:
Jul 2022
Historique:
revised: 20 11 2021
received: 15 08 2021
accepted: 04 01 2022
pubmed: 12 4 2022
medline: 20 7 2022
entrez: 11 4 2022
Statut: ppublish

Résumé

Since the discovery of calbindin release into the urine during renal injury, there has been growing interest in the utility of this protein as a biomarker of nephrotoxicity. However, little is known about the intrarenal regulation of the release and expression of this calcium-regulating protein during kidney injury. We sought to characterize the time-dependent expression and excretion of the protein calbindin in the distal tubule in comparison to kidney injury molecule-1 (Kim-1), a protein in the proximal tubule, in mice treated with cisplatin. Urine, blood, and kidneys were collected from male C57BL/6 mice treated with vehicle or cisplatin (20 mg/kg ip). Urinary concentrations of calbindin and Kim-1 were elevated by 11.6-fold and 2.5-fold, respectively, within 2 days after cisplatin. Circulating creatinine and blood urea nitrogen levels increased in cisplatin-treated mice by 3 days, confirming the development of acute kidney injury. Time-dependent decreases in intrarenal calbindin protein were observed on Days 3 and 4 and a 200-fold upregulation of calbindin (CALB1) and KIM-1 messenger RNAs (mRNAs) was observed on Day 3. These data suggest that early loss of calbindin protein into the urine along with declines in renal calbindin levels initiates a compensatory induction of mRNA expression at later time points (Days 3 and 4). Understanding the regulation of calbindin during cisplatin nephrotoxicity further enhances its utility as a potential urinary biomarker of kidney damage. The results of the current study support the combined use of a proximal (Kim-1) and distal tubule (calbindin) marker to phenotype acute kidney injury secondary to cisplatin administration.

Identifiants

pubmed: 35403300
doi: 10.1002/jbt.23068
pmc: PMC9296602
mid: NIHMS1793909
doi:

Substances chimiques

Antineoplastic Agents 0
Biomarkers 0
Calbindins 0
Cisplatin Q20Q21Q62J

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

e23068

Subventions

Organisme : NIEHS NIH HHS
ID : ES007148
Pays : United States
Organisme : NCI NIH HHS
ID : CA046934
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM123330
Pays : United States
Organisme : NIEHS NIH HHS
ID : ES005022
Pays : United States
Organisme : NIDDK NIH HHS
ID : DK093903
Pays : United States
Organisme : NIGMS NIH HHS
ID : GM123330
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA072720
Pays : United States
Organisme : NIEHS NIH HHS
ID : T32 ES007148
Pays : United States
Organisme : NIDDK NIH HHS
ID : R21 DK093903
Pays : United States
Organisme : NIEHS NIH HHS
ID : P30 ES005022
Pays : United States
Organisme : NCI NIH HHS
ID : CA072720
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA046934
Pays : United States

Informations de copyright

© 2022 Wiley Periodicals LLC.

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Auteurs

Blessy George (B)

Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, New Jersey, USA.

John T Szilagyi (JT)

Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, New Jersey, USA.

Melanie S Joy (MS)

Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Aurora, Colorado, USA.
Division of Developmental Therapeutics, Cancer Center, University of Colorado, Aurora, Colorado, USA.
Division of Renal Diseases and Hypertension, University of Colorado School of Medicine, Aurora, Colorado, USA.

Lauren M Aleksunes (LM)

Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, New Jersey, USA.
Division of Toxicology, Environmental and Occupational Health Sciences Institute, Rutgers University, Piscataway, New Jersey​, USA.

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Classifications MeSH