Exosomal MALAT1 from macrophages treated with high levels of glucose upregulates LC3B expression via miR-204-5p downregulation

Sep 29, 2026

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Diabetes-related complications involve metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), yet macrophage-derived MALAT1’s impact on autophagy during hyperglycemia remains unclear. This study examined molecular regulation by exposing macrophages to 25 mM glucose, isolating secreted exosomes, and evaluating vascular injury effects in a rat carotid balloon model. Methods included RT-qPCR, western blotting, immunohistochemistry, and luciferase assays. Hyperglycemia increased MALAT1 in macrophage exosomes and promoted LC3B via suppression of miR-204-5p, implicating an exosomal MALAT1/miR-204-5p/LC3B axis in vascular disease.

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Abstract

Background

Methods

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Conclusion

J Chin MedAssoc Original article Exosomal MALAT1 from macrophages treated with high levels of glucose upregulates LC3B expression via miR-204-5p downregulation Kou-Gi Shyua,*, Bao-Wei Wangb, Chun-Ming Panb, Wei-Jen Fangb, Chiu-Mei Linc,d aDivision of Cardiology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan, ROC; bDepartment of Research, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan, ROC; cDepartment of Emergency Medicine, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan, ROC; dSchool of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan, ROC Abstract Background: Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) plays a critical role in the pathophysiology of diabetes-related complications. However, whether macrophage-derived MALAT1 affects autophagic activity under hyperglycemic conditions is unclear. Therefore, we investigated the molecular regulatory mechanisms of macrophage-derived MALAT1 and autophagy under hyperglycemic conditions. Methods: Hyperglycemia was induced by culturing macrophages in 25 mM glucose for 1 hour. Exosomes were extracted from the culture media. A rat model of carotid artery balloon injury was established to assess the effect of MALAT1 on vascular injury. Reverse transcription, real-time quantitative polymerase chain reaction, western blotting, immunohistochemical staining, and luciferase activity assays were performed. Results: Stimulation with high levels of glucose significantly enhanced MALAT1 expression in macrophage-derived exosomes. MALAT1 inhibited miR-204-5p expression in macrophage-derived exosomes under hyperglycemic conditions. siRNA-induced silencing of MALAT1 significantly reversed macrophage-derived exosome-induced miR-204-5p expression. Hyperglycemic treatment caused a significant, exosome-induced increase in the expression of the autophagy marker LC3B in macrophages. Silencing MALAT1 and overexpression of miR-204-5p significantly decreased LC3B expression induced by macrophage-derived exosomes. Overexpression of miR-204-5p significantly reduced LC3B luciferase activity induced by macrophage-derived exosomes. Balloon injury to the carotid artery in rats significantly enhanced MALAT1 and LC3B expression, and significantly reduced miR-204-5p expression in carotid artery tissue. Silencing MALAT1 significantly reversed miR-204-5p expression in carotid artery tissue after balloon injury. MALAT1 silencing or miR-204-5p overexpression significantly reduced LC3B expression after balloon injury. Conclusion: This study demonstrated that hyperglycemia upregulates MALAT1 . MALAT1 suppresses miR-204-5p expression and counteracts the inhibitory effect of miR-204-5p on LC3B expression in macrophages to promote vascular disease. Keywords: Autophagy; Exosomes; Macrophage; MALAT1 ; Rat 1. INTRODUCTION Autophagy is a key catabolic process that promotes cell survival by protecting cells from different types of stress. It plays an important role in cellular quality control and homeostasis under both normal and pathologic conditions.1 Autophagy activity is strongly linked to cardiovascular development and preservation of cardiac and vascular homeostasis, as well asthe onset and progression of cardiovascular diseases (CVDs) .2,3 Increasing evidence has shown that macrophage autophagy plays a crucial role in inflammation, apoptosis, and cholesterol * Address correspondence. Dr. Kou-Gi Shyu, Division of Cardiology, Shin Kong Wu Ho-Su Memorial Hospital, 95, Wen-Chang Road, Taipei 111, Taiwan ROC. E-mail address: shyukg@ms12.hinet.net (K.-G. Shyu). Conflicts of interest: The authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article. Journal of Chinese Medical Association. (2024) 87: 581-589. Received October 16, 2023; accepted March 22, 2024. doi: 10. 1097/JCMA.0000000000001098 Copyright © 2024, the Chinese Medical Association. This is an open access article under the CC

FAQs

How was hyperglycemia modeled in the study?

Macrophages were cultured in 25 mM glucose for 1 hour to induce hyperglycemic conditions before exosome extraction and downstream analyses.

What role does miR-204-5p play in the MALAT1–LC3B pathway?

High glucose increased MALAT1 in macrophage-derived exosomes while MALAT1 suppressed miR-204-5p expression; elevating miR-204-5p reduced LC3B expression and luciferase activity triggered by the exosomes.

What evidence links the mechanism to vascular injury?

In rats, carotid artery balloon injury increased MALAT1 and LC3B and decreased miR-204-5p in tissue; silencing MALAT1 or overexpressing miR-204-5p reduced LC3B after injury.

Sep 29, 2026

Uploaded by Asher