Exosomal MALAT1 from Rapid Electrical Stimulation-Treated Atrial Fibroblasts Activates Autophagy by Downregulating miR-204-5p and Upregulating LC3B.
SK, C., BW, W., YJ, Y., WJ, F., CM, L., CY, C., & KG, S. (2026). Exosomal MALAT1 from Rapid Electrical Stimulation-Treated Atrial Fibroblasts Activates Autophagy by Downregulating miR-204-5p and Upregulating LC3B.. Cells. https://doi.org/10.3390/cells15121126
SK C, BW W, YJ Y, WJ F, CM L, CY C, et al. Exosomal MALAT1 from Rapid Electrical Stimulation-Treated Atrial Fibroblasts Activates Autophagy by Downregulating miR-204-5p and Upregulating LC3B.. Cells. 2026; doi: 10.3390/cells15121126
SK C, BW W, YJ Y, et al. Exosomal MALAT1 from Rapid Electrical Stimulation-Treated Atrial Fibroblasts Activates Autophagy by Downregulating miR-204-5p and Upregulating LC3B.[J]. Cells. 2026. DOI: 10.3390/cells15121126.
@article{sk2026,
author = {Chua SK and Wang BW and Yu YJ and Fang WJ and Lin CM and Chuang CY and Shyu KG},
title = {Exosomal MALAT1 from Rapid Electrical Stimulation-Treated Atrial Fibroblasts Activates Autophagy by Downregulating miR-204-5p and Upregulating LC3B.},
journal = {Cells},
year = {2026},
doi = {10.3390/cells15121126},
note = {PMID: 42346153},
}
TY - JOUR AU - Chua SK AU - Wang BW AU - Yu YJ AU - Fang WJ AU - Lin CM AU - Chuang CY AU - Shyu KG TI - Exosomal MALAT1 from Rapid Electrical Stimulation-Treated Atrial Fibroblasts Activates Autophagy by Downregulating miR-204-5p and Upregulating LC3B. T2 - Cells PY - 2026 DO - 10.3390/cells15121126 AN - PMID:42346153 ER -
Background: Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and is strongly associated with atrial structural remodeling driven by activated cardiac fibroblasts. Autophagy has been implicated in AF-related atrial remodeling; however, the non-coding RNA mechanisms that govern autophagic activation in atrial fibroblasts under rapid electrical stress remain poorly understood. Methods: Human cardiac fibroblasts from adult atria (HCF-aa) were subjected to rapid electrical stimulation (RES) at 0.5 V/cm and 10 Hz. Expression levels of exosomal metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), cytoplasmic miR-204-5p, and microtubule-associated protein light chain 3B (LC3B) were measured using quantitative real-time PCR and Western blot analyses. Luciferase reporter assays were performed to confirm direct molecular interactions. The functional roles of MALAT1 siRNA, miR-204-5p mimics/antagomirs, rapamycin, and 3-methyladenine (3-MA) on LC3B expression and autophagic activation were assessed by Western blot and immunofluorescence confocal microscopy for LC3B puncta formation. Results: RES significantly induced exosomal MALAT1 expression in a voltage- and time-dependent manner, peaking at 2 h post-stimulation, while cytoplasmic MALAT1 levels remained unchanged. Cytoplasmic miR-204-5p exhibited an initial transient rise followed by a significant decline at 2 h, inversely correlating with peak MALAT1 levels. LC3B mRNA and protein expression subsequently increased, peaking at 6 and 16 h, respectively. Luciferase reporter assays confirmed that miR-204-5p directly binds both the MALAT1 transcript and the 3'-UTR of LC3B mRNA. MALAT1 knockdown augmented miR-204-5p levels and suppressed LC3B expression, while miR-204-5p overexpression attenuated RES-induced LC3B upregulation and LC3B puncta accumulation. Conversely, miR-204-5p inhibition further enhanced autophagic activation, as evidenced by increased LC3B puncta density. Conclusions: In HCF-aa subjected to RES, MALAT1 functions intracellularly as a competing endogenous RNA to putatively sequester miR-204-5p, thereby de-repressing LC3B expression and promoting autophagic activation. Concurrent exosomal secretion of MALAT1 may additionally serve as a paracrine signal to neighboring cells, though this requires future conditioned-media transfer experiments to confirm.