PDCD4 promotes inflammation/fibrosis by activating the PPARγ/NFκB pathway in mouse atrial myocytes.
Mol Med Rep
; 30(5)2024 11.
Article
in En
| MEDLINE
| ID: mdl-39301631
ABSTRACT
Fibrosis is the basis of structural remodeling in atrial fibrillation (AF), during which inflammation is crucial. Programmed cell death factor 4 (PDCD4) is a newly identified inflammatory gene, with unknown mechanisms of action in AF. The present study aimed to elucidate the effects of PDCD4 on the inflammation and structural remodeling of atrial myocytes. For this purpose, a PDCD4 overexpression plasmid (oePDCD4) and PDCD4 small interfering (si)RNA (siPDCD4) were used to modulate PDCD4 expression in mouse atrial myocytes (HL1 cells). The expression of PDCD4 was detected using reverse transcriptionquantitative PCR and western blot analysis. The optimal drug concentrations of peroxisome proliferatoractivated receptor γ (PPARγ) agonist (pioglitazone hydrochloride), NFκB inhibitor (CBL0137), PPARγ inhibitor (GW9962) and NFκB agonist (betulinic acid) were screened using a Cell Counting Kit8 assay. The levels of inflammatory factors were detected using enzymelinked immunosorbent assays, the expression levels of fibrosisrelated proteins and NFκB subunits were detected using western blot analysis, and the expression of phosphorylated (p)p65/p65 was detected using immunofluorescence staining. The results revealed that PDCD4 overexpression increased the levels of fibrotic factors (collagen I, collagen III, fibronectin, αsmooth muscle actin and matrix metalloproteinase 2), proinflammatory cytokines (IFNγ, IL6, IL17A and TNFα) and pp65, whereas it reduced the levels of antiinflammatory cytokines (IL4) in HL1 cells. Additionally, treatment with the PPARγ agonist and NFκB inhibitor reversed the levels of fibrotic, proinflammatory and antiinflammatory factors in oePDCD4HL1 cells. By contrast, PDCD4 silencing exerted the opposite effects on fibrotic factors, proinflammatory cytokines, antiinflammatory cytokines and pp65. In addition, treatment with the PPARγ inhibitor and NFκB agonist reversed the levels of fibrotic, proinflammatory and antiinflammatory factors in siPDCD4HL1 cells. In conclusion, the present study demonstrated that PDCD4 may induce inflammation and fibrosis by activating the PPARγ/NFκB signaling pathway, thereby promoting the structural remodeling of atrial myocytes in AF.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Fibrosis
/
Signal Transduction
/
NF-kappa B
/
RNA-Binding Proteins
/
Myocytes, Cardiac
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PPAR gamma
/
Apoptosis Regulatory Proteins
/
Inflammation
Limits:
Animals
Language:
En
Journal:
Mol Med Rep
Year:
2024
Document type:
Article
Country of publication:
Grecia