PDCD4 promotes inflammation/fibrosis by activating the PPAR‑&gamma;/NF‑&kappa;B pathway in mouse atrial myocytes

Yu,Li; Yang,Yuchun; Wang,Jiao; Bao,Zhen; Zheng,Meijuan; Wang,Xi; Zhu,Yu; Wulasihan,Muhuyati

doi:10.3892/mmr.2024.13333

PDCD4 promotes inflammation/fibrosis by activating the PPAR‑γ/NF‑κB pathway in mouse atrial myocytes

Authors:
- Li Yu
- Yuchun Yang
- Jiao Wang
- Zhen Bao
- Meijuan Zheng
- Xi Wang
- Yu Zhu
- Muhuyati Wulasihan
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Affiliations: Department of Integrated Cardiology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830000, P.R. China, School of Health Management, Xinjiang Medical University, Urumqi, Xinjiang 830054, P.R. China
Published online on: September 19, 2024 https://doi.org/10.3892/mmr.2024.13333
Article Number: 209
Copyright: © Yu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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 (HL‑1 cells). The expression of PDCD4 was detected using reverse transcription‑quantitative PCR and western blot analysis. The optimal drug concentrations of peroxisome proliferator‑activated receptor γ (PPARγ) agonist (pioglitazone hydrochloride), NF‑κB inhibitor (CBL0137), PPARγ inhibitor (GW9962) and NF‑κB agonist (betulinic acid) were screened using a Cell Counting Kit‑8 assay. The levels of inflammatory factors were detected using enzyme‑linked immunosorbent assays, the expression levels of fibrosis‑related proteins and NF‑κB 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, α‑smooth muscle actin and matrix metalloproteinase 2), pro‑inflammatory cytokines (IFN‑γ, IL‑6, IL‑17A and TNF‑α) and p‑p65, whereas it reduced the levels of anti‑inflammatory cytokines (IL‑4) in HL‑1 cells. Additionally, treatment with the PPARγ agonist and NF‑κB inhibitor reversed the levels of fibrotic‑, pro‑inflammatory and anti‑inflammatory factors in oePDCD4‑HL‑1 cells. By contrast, PDCD4 silencing exerted the opposite effects on fibrotic factors, pro‑inflammatory cytokines, anti‑inflammatory cytokines and p‑p65. In addition, treatment with the PPARγ inhibitor and NF‑κB agonist reversed the levels of fibrotic‑, pro‑inflammatory and anti‑inflammatory factors in siPDCD4‑HL‑1 cells. In conclusion, the present study demonstrated that PDCD4 may induce inflammation and fibrosis by activating the PPARγ/NF‑κB signaling pathway, thereby promoting the structural remodeling of atrial myocytes in AF.

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