Fatty Acid Binding Protein-4 Silencing Inhibits Ferroptosis to Alleviate Lipopolysaccharide-induced Injury of Renal Tubular Epithelial Cells by Blocking Janus Kinase 2/Signal Transducer and Activator of Transcription 3 Signaling.

Publisher: Wolters Kluwer - Medknow Country of Publication: India NLM ID: 9918803386606676 Publication Model: Print-Electronic Cited Medium: Print ISSN: 2950-6344 (Print) Linking ISSN: 29506344 NLM ISO Abbreviation: J Physiol Investig Subsets: MEDLINE

Original Publication: [Mumbai] : Wolters Kluwer - Medknow, [2024]-

Epithelial Cells*/metabolism ; Epithelial Cells*/drug effects ; Epithelial Cells*/pathology ; Fatty Acid-Binding Proteins*/metabolism ; Fatty Acid-Binding Proteins*/genetics ; Ferroptosis*/drug effects ; Janus Kinase 2*/metabolism ; Kidney Tubules*/pathology ; Kidney Tubules*/metabolism ; Kidney Tubules*/drug effects ; Signal Transduction*/drug effects ; STAT3 Transcription Factor*/metabolism ; STAT3 Transcription Factor*/genetics; Humans ; Acute Kidney Injury/metabolism ; Acute Kidney Injury/genetics ; Acute Kidney Injury/pathology ; Acute Kidney Injury/chemically induced ; Cell Line ; Lipopolysaccharides/toxicity

Sepsis-induced kidney injury (SAKI) has been frequently established as a prevailing complication of sepsis which is linked to unfavorable outcomes. Fatty acid-binding protein-4 (FABP4) has been proposed as a possible target for the treatment of SAKI. In the current work, we aimed to explore the role and underlying mechanism of FABP4 in lipopolysaccharide (LPS)-induced human renal tubular epithelial cell damage. In LPS-induced human kidney 2 (HK2) cells, FABP4 expression was tested by the reverse transcription-quantitative polymerase chain reaction and Western blot. Cell counting kit-8 method assayed cell viability. Inflammatory levels were detected using the enzyme-linked immunosorbent assay. Immunofluorescence staining measured the nuclear translocation of nuclear factor kappa B p65. Thiobarbituric acid-reactive substances assay and C11 BODIPY 581/591 probe were used to estimate the level of cellular lipid peroxidation. Fe2+ content was examined by the kit. In addition, the expression of proteins related to inflammation-, ferroptosis- and Janus kinase 2 (JAK2)/signal transducer, and activator of transcription 3 (STAT3) signaling was detected by the Western blot analysis. The results revealed that FABP4 was significantly upregulated in LPS-treated HK2 cells, the knockdown of which elevated the viability, whereas alleviated the inflammation and ferroptosis in HK2 cells challenged with LPS. In addition, down-regulation of FABP4 inactivated JAK2/STAT3 signaling. JAK2/STAT3 stimulator (colivelin) and ferroptosis activator (Erastin) partially restored the effects of FABP4 interference on LPS-triggered inflammation and ferroptosis in HK2 cells. Together, FABP4 knockdown inhibited ferroptosis to alleviate LPS-induced injury of renal tubular epithelial cells through suppressing JAK2/STAT3 signaling.
(Copyright © 2024 Copyright: © 2024 Journal of Physiological Investigation.)

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0 (FABP4 protein, human)
0 (Fatty Acid-Binding Proteins)
EC 2.7.10.2 (JAK2 protein, human)
EC 2.7.10.2 (Janus Kinase 2)
0 (Lipopolysaccharides)
0 (STAT3 protein, human)
0 (STAT3 Transcription Factor)

Date Created: 20240523 Date Completed: 20240523 Latest Revision: 20240903

20240904

10.4103/EJPI.EJPI-D-23-00027

38780272