CUX1 attenuates the apoptosis of renal tubular epithelial cells induced by contrast media through activating the PI3K/AKT signaling pathway.
Humans
Apoptosis
/ drug effects
Signal Transduction
/ drug effects
Contrast Media
/ adverse effects
Proto-Oncogene Proteins c-akt
/ metabolism
Phosphatidylinositol 3-Kinases
/ metabolism
Epithelial Cells
/ metabolism
Homeodomain Proteins
/ metabolism
Acute Kidney Injury
/ metabolism
Kidney Tubules
/ pathology
Cell Line
Transcription Factors
/ metabolism
Male
Iohexol
Female
Cell Proliferation
/ drug effects
Middle Aged
Repressor Proteins
CUT-like homeobox 1 (CUX1)
Contrast media (CM)
Contrast-induced acute kidney injury
PI3K/AKT signaling pathway
Renal tubular epithelial cells
Journal
BMC nephrology
ISSN: 1471-2369
Titre abrégé: BMC Nephrol
Pays: England
ID NLM: 100967793
Informations de publication
Date de publication:
07 Jun 2024
07 Jun 2024
Historique:
received:
29
06
2023
accepted:
28
05
2024
medline:
8
6
2024
pubmed:
8
6
2024
entrez:
7
6
2024
Statut:
epublish
Résumé
Contrast media (CM) is a commonly applied drug in medical examination and surgery. However, contrast-induced acute kidney injury (CIAKI) poses a severe threat to human life and health. Notably, the CUT-like homeobox 1 (CUX1) gene shows protective effects in a variety of cells. Therefore, the objective of this study was to provide a new target for the treatment of CIAKI through exploring the role and possible molecular mechanism of CUX1 in CIAKI. Blood samples were collected from 20 patients with CIAKI and healthy volunteers. Human kidney 2 (HK-2) cells were incubated with 200 mg/mL iohexol for 6 h to establish a contrast-induced injury model of HK-2 cells. Subsequently, qRT-PCR was used to detect the relative mRNA expression of CUX1; CCK-8 and flow cytometry to assess the proliferation and apoptosis of HK-2 cells; the levels of IL(interleukin)-1β, tumor necrosis factor alpha (TNF-α) and malondialdehyde (MDA) in cells and lactate dehydrogenase (LDH) activity in cell culture supernatant were detect; and western blot to observe the expression levels of CUX1 and the PI3K/AKT signaling pathway related proteins [phosphorylated phosphoinositide 3-kinase (p-PI3K), PI3K, phosphorylated Akt (p-AKT), AKT]. CUX1 expression was significantly downregulated in blood samples of patients with CIAKI and contrast-induced HK-2 cells. Contrast media (CM; iohexol) treatment significantly reduced the proliferation of HK-2 cells, promoted apoptosis, stimulated inflammation and oxidative stress that caused cell damage. CUX1 overexpression alleviated cell damage by significantly improving the proliferation level of HK-2 cells induced by CM, inhibiting cell apoptosis, and reducing the level of LDH in culture supernatant and the expression of IL-1β, TNF-α and MDA in cells. CM treatment significantly inhibited the activity of PI3K/AKT signaling pathway activity. Nevertheless, up-regulating CUX1 could activate the PI3K/AKT signaling pathway activity in HK-2 cells induced by CM. CUX1 promotes cell proliferation, inhibits apoptosis, and reduces inflammation and oxidative stress in CM-induced HK-2 cells to alleviate CM-induced damage. The mechanism of CUX1 may be correlated with activation of the PI3K/AKT signaling pathway.
Identifiants
pubmed: 38849771
doi: 10.1186/s12882-024-03625-8
pii: 10.1186/s12882-024-03625-8
doi:
Substances chimiques
Contrast Media
0
Proto-Oncogene Proteins c-akt
EC 2.7.11.1
Phosphatidylinositol 3-Kinases
EC 2.7.1.-
Homeodomain Proteins
0
CUX1 protein, human
0
Transcription Factors
0
Iohexol
4419T9MX03
Repressor Proteins
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
192Informations de copyright
© 2024. The Author(s).
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