FGF21 is induced in cisplatin nephrotoxicity to protect against kidney tubular cell injury

Fanghua Li, Zhiwen Liu, Chengyuan Tang, Juan Cai, Zheng Dong

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Cisplatin, awidely used cancer therapy drug, induces nephrotoxicity or acute kidney injury (AKI), but the underlying mechanism remains unclear, and renal protective approaches are not available. Fibroblast growth factor (FGF)21 is an endocrine factor that regulates glucose uptake, metabolism, and energy expenditure. However, recent work has also implicated FGF21 in cellular stress response under pathogenic conditions. The role and regulation of FGF21 in AKI are unclear. Here, we show that FGF21 was dramatically induced during cisplatin treatment of renal tubular cells in vitro and mouse kidneys in vivo. The inductive response was suppressed by pifithrin (a pharmacological inhibitor of P53), suggesting a role of P53 in FGF21 induction. In cultured renal tubular cells, knockdown of FGF21 aggravated cisplatin-induced apoptosis, whereas supplementation of recombinant FGF21 was protective. Consistently, recombinant FGF21 alleviated cisplatin-induced kidney dysfunction, tissue damage, and tubular apoptosis in mice.Mechanistically, FGF21 suppressed P53 induction and activation during cisplatin treatment. Together, these results indicate that FGF21 is induced during cisplatin nephrotoxicity to protect renal tubules, and recombinant FGF21 may have therapeutic potential.

Original languageEnglish (US)
Pages (from-to)3423-3433
Number of pages11
JournalFASEB Journal
Volume32
Issue number6
DOIs
StatePublished - Jun 1 2018

Fingerprint

Cisplatin
Kidney
Wounds and Injuries
Acute Kidney Injury
fibroblast growth factor 21
Apoptosis
Drug therapy
Metabolism
Energy Metabolism
Therapeutics
Chemical activation
Cells
Pharmacology
Tissue
Glucose
Drug Therapy

Keywords

  • Acute kidney injury
  • Apoptosis
  • P53

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

Cite this

FGF21 is induced in cisplatin nephrotoxicity to protect against kidney tubular cell injury. / Li, Fanghua; Liu, Zhiwen; Tang, Chengyuan; Cai, Juan; Dong, Zheng.

In: FASEB Journal, Vol. 32, No. 6, 01.06.2018, p. 3423-3433.

Research output: Contribution to journalArticle

Li, Fanghua ; Liu, Zhiwen ; Tang, Chengyuan ; Cai, Juan ; Dong, Zheng. / FGF21 is induced in cisplatin nephrotoxicity to protect against kidney tubular cell injury. In: FASEB Journal. 2018 ; Vol. 32, No. 6. pp. 3423-3433.
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