---
title: "EV-encapsulated miRNAs drive monocyte–endothelial crosstalk and worsen renal injury in diabetic ki"
id: "pubmed-42275918"
canonical_url: "https://medichelpline.com/clinical-feed/pubmed-42275918"
content_type: "clinical_feed_article"
specialty: "Pharmacology"
source_name: "PubMed / NCBI"
source_url: "https://pubmed.ncbi.nlm.nih.gov/42275918/"
doi: "10.1016/j.intimp.2026.116960"
published_at: "2026-09-15T00:00:00.000Z"
evidence_level: "Journal Article"
license: "CC-BY-NC-4.0 / Informational Use"
---
# EV-encapsulated miRNAs drive monocyte–endothelial crosstalk and worsen renal injury in diabetic ki
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/pubmed-42275918
- **Specialty:** [Pharmacology](https://medichelpline.com/clinical-feed/pharmacology.md)
- **Primary Source:** PubMed / NCBI
- **Source URL:** [Original Journal Publication](https://pubmed.ncbi.nlm.nih.gov/42275918/)
- **DOI:** [10.1016/j.intimp.2026.116960](https://doi.org/10.1016%2Fj.intimp.2026.116960)
- **Published At:** 2026-09-15T00:00:00.000Z
- **Evidence Rating:** Journal Article
## Executive GIST (TL;DR)
- Diabetic kidney disease (DKD) features microcirculatory dysfunction and immune-mediated injury; the study investigates whether **extracellular vesicle (EV)**-encapsulated microRNAs mediate crosstalk between endothelial cells (ECs) and monocytes in DKD. - EVs were isolated from monocytes and ECs exposed to normal- and high-glucose conditions; EV characterization and miRNA screening identified differentially expressed miRNAs associated with high glucose. - Functional assays included RNase/Triton treatments to confirm miRNA localization in EVs, dual-luciferase reporter assays to validate miRNA targets, and gain- and loss-of-function and rescue experiments performed both in vitro and in vivo. - Under high-glucose conditions, monocyte-derived EVs aggravated endothelial injury by delivering increased **miR-191-3p**, which targets **CYLD** and activates the **NF-κB** signaling pathway. - Endothelial-derived EVs from high-glucose conditions promoted monocyte inflammation and adhesion by decreasing **miR-615-3p**, leading to upregulation of **IFNGR2** and activation of the **STAT3** pathway. - Targeted interventions against these key molecules reduced cellular injury in vitro and partially ameliorated renal damage in vivo, supporting their functional relevance in DKD pathogenesis. - The authors define two core regulatory axes: **miR-191-3p/CYLD/NF-κB** and **miR-615-3p/IFNGR2/STAT3**, linking microcirculatory dysfunction and immune injury in DKD. - The study notes that the diagnostic and therapeutic potential of these EV-miRNAs requires further validation; specific experimental details, quantitative results, and broader clinical validation were not reported in the abstract.
## Clinical Analysis & Structured Key Points
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Epub 2026 Jun 11. # Extracellular vesicle-encapsulated miRNAs mediate monocyte-endothelial cell crosstalk to exacerbate renal injury in diabetic kidney disease [Jiaxing Jing](https://pubmed.ncbi.nlm.nih.gov/?term=Jing+J&cauthor_id=42275918)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42275918/#full-view-affiliation-1 "Hebei University of Chinese Medicine, Shijiazhuang 050200, China."), [Jiasheng An](https://pubmed.ncbi.nlm.nih.gov/?term=An+J&cauthor_id=42275918)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42275918/#full-view-affiliation-1 "Hebei University of Chinese Medicine, Shijiazhuang 050200, China."), [Xiangmei Chen](https://pubmed.ncbi.nlm.nih.gov/?term=Chen+X&cauthor_id=42275918)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42275918/#full-view-affiliation-2 "Department of Nephrology, First Medical Center of Chinese PLA General Hospital, Beijing 100853, China; National Key Laboratory of Kidney Diseases, Beijing 100853, China; National Clinical Research Center for Kidney Diseases, Beijing 100853, China; Beijing Key Laboratory of Kidney Disease Research, Beijing 100853, China."), [Bin Cong](https://pubmed.ncbi.nlm.nih.gov/?term=Cong+B&cauthor_id=42275918)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42275918/#full-view-affiliation-3 "Hebei Medical University, Shijiazhuang 050017, China; Hebei Key Laboratory of Forensic Medicine, Shijiazhuang 050017, China."), [Wentao Yu](https://pubmed.ncbi.nlm.nih.gov/?term=Yu+W&cauthor_id=42275918)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42275918/#full-view-affiliation-4 "Hebei University of Chinese Medicine, Shijiazhuang 050200, China; Hebei Key Laboratory of Chinese Medicine Research on Cardio-Cerebrovascular Diseases, Shijiazhuang 050091, China; Hebei International Joint Research Center for Dominant Diseases in Chinese Medicine and Acupuncture, Shijiazhuang 050091, China. Electronic address: yuwentao@hebcm.edu.cn."), [Weijuan Gao](https://pubmed.ncbi.nlm.nih.gov/?term=Gao+W&cauthor_id=42275918)[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42275918/#full-view-affiliation-5 "Hebei University of Chinese Medicine, Shijiazhuang 050200, China; Hebei Key Laboratory of Chinese Medicine Research on Cardio-Cerebrovascular Diseases, Shijiazhuang 050091, China. Electronic address: gwj6088@163.com.") Affiliations Expand ### Affiliations * 1 Hebei University of Chinese Medicine, Shijiazhuang 050200, China. * 2 Department of Nephrology, First Medical Center of Chinese PLA General Hospital, Beijing 100853, China; National Key Laboratory of Kidney Diseases, Beijing 100853, China; National Clinical Research Center for Kidney Diseases, Beijing 100853, China; Beijing Key Laboratory of Kidney Disease Research, Beijing 100853, China. * 3 Hebei Medical University, Shijiazhuang 050017, China; Hebei Key Laboratory of Forensic Medicine, Shijiazhuang 050017, China. * 4 Hebei University of Chinese Medicine, Shijiazhuang 050200, China; Hebei Key Laboratory of Chinese Medicine Research on Cardio-Cerebrovascular Diseases, Shijiazhuang 050091, China; Hebei International Joint Research Center for Dominant Diseases in Chinese Medicine and Acupuncture, Shijiazhuang 050091, China. Electronic address: yuwentao@hebcm.edu.cn. * 5 Hebei University of Chinese Medicine, Shijiazhuang 050200, China; Hebei Key Laboratory of Chinese Medicine Research on Cardio-Cerebrovascular Diseases, Shijiazhuang 050091, China. Electronic address: gwj6088@163.com. * PMID: **42275918** * DOI: [ 10.1016/j.intimp.2026.116960 ](https://doi.org/10.1016/j.intimp.2026.116960) Item in Clipboard # Extracellular vesicle-encapsulated miRNAs mediate monocyte-endothelial cell crosstalk to exacerbate renal injury in diabetic kidney disease Jiaxing Jing et al. Int Immunopharmacol. 2026. Show details Display options Display options Format Abstract PubMed PMID Int Immunopharmacol Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Int+Immunopharmacol%22%5Bjour%5D&sort=date&sort_order=desc) * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22Int+Immunopharmacol%22%5BTitle+Abbreviation%5D) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42275918/) . 2026 Sep 15:185:116960. doi: 10.1016/j.intimp.2026.116960. Epub 2026 Jun 11. ### Authors [Jiaxing Jing](https://pubmed.ncbi.nlm.nih.gov/?term=Jing+J&cauthor_id=42275918)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42275918/#short-view-affiliation-1 "Hebei University of Chinese Medicine, Shijiazhuang 050200, China."), [Jiasheng An](https://pubmed.ncbi.nlm.nih.gov/?term=An+J&cauthor_id=42275918)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42275918/#short-view-affiliation-1 "Hebei University of Chinese Medicine, Shijiazhuang 050200, China."), [Xiangmei Chen](https://pubmed.ncbi.nlm.nih.gov/?term=Chen+X&cauthor_id=42275918)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42275918/#short-view-affiliation-2 "Department of Nephrology, First Medical Center of Chinese PLA General Hospital, Beijing 100853, China; National Key Laboratory of Kidney Diseases, Beijing 100853, China; National Clinical Research Center for Kidney Diseases, Beijing 100853, China; Beijing Key Laboratory of Kidney Disease Research, Beijing 100853, China."), [Bin Cong](https://pubmed.ncbi.nlm.nih.gov/?term=Cong+B&cauthor_id=42275918)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42275918/#short-view-affiliation-3 "Hebei Medical University, Shijiazhuang 050017, China; Hebei Key Laboratory of Forensic Medicine, Shijiazhuang 050017, China."), [Wentao Yu](https://pubmed.ncbi.nlm.nih.gov/?term=Yu+W&cauthor_id=42275918)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42275918/#short-view-affiliation-4 "Hebei University of Chinese Medicine, Shijiazhuang 050200, China; Hebei Key Laboratory of Chinese Medicine Research on Cardio-Cerebrovascular Diseases, Shijiazhuang 050091, China; Hebei International Joint Research Center for Dominant Diseases in Chinese Medicine and Acupuncture, Shijiazhuang 050091, China. Electronic address: yuwentao@hebcm.edu.cn."), [Weijuan Gao](https://pubmed.ncbi.nlm.nih.gov/?term=Gao+W&cauthor_id=42275918)[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42275918/#short-view-affiliation-5 "Hebei University of Chinese Medicine, Shijiazhuang 050200, China; Hebei Key Laboratory of Chinese Medicine Research on Cardio-Cerebrovascular Diseases, Shijiazhuang 050091, China. Electronic address: gwj6088@163.com.") ### Affiliations * 1 Hebei University of Chinese Medicine, Shijiazhuang 050200, China. * 2 Department of Nephrology, First Medical Center of Chinese PLA General Hospital, Beijing 100853, China; National Key Laboratory of Kidney Diseases, Beijing 100853, China; National Clinical Research Center for Kidney Diseases, Beijing 100853, China; Beijing Key Laboratory of Kidney Disease Research, Beijing 100853, China. * 3 Hebei Medical University, Shijiazhuang 050017, China; Hebei Key Laboratory of Forensic Medicine, Shijiazhuang 050017, China. * 4 Hebei University of Chinese Medicine, Shijiazhuang 050200, China; Hebei Key Laboratory of Chinese Medicine Research on Cardio-Cerebrovascular Diseases, Shijiazhuang 050091, China; Hebei International Joint Research Center for Dominant Diseases in Chinese Medicine and Acupuncture, Shijiazhuang 050091, China. Electronic address: yuwentao@hebcm.edu.cn. * 5 Hebei University of Chinese Medicine, Shijiazhuang 050200, China; Hebei Key Laboratory of Chinese Medicine Research on Cardio-Cerebrovascular Diseases, Shijiazhuang 050091, China. Electronic address: gwj6088@163.com. * PMID: **42275918** * DOI: [ 10.1016/j.intimp.2026.116960 ](https://doi.org/10.1016/j.intimp.2026.116960) Item in Clipboard Full text links Cite Display options Display options Format Abstract PubMed PMID ## Abstract **Background:** Diabetic kidney disease (DKD) is a major microvascular complication of diabetes, with microcirculatory dysfunction and immune injury as its core pathological features. Extracellular vesicles (EVs) act as key mediators of intercellular communication, but it remains unclear whether EV-encapsulated microRNAs (miRNAs) are involved in the crosstalk between endothelial cells (ECs) and monocytes in DKD. **Methods:** EVs were isolated from monocytes and ECs under normal-glucose and high-glucose conditions. After characterization of EVs, differentially expressed miRNAs were screened. RNase/Triton functional assays, dual-luciferase reporter assays, gain- and loss-of-function experiments, and rescue experiments were further performed to validate the regulatory mechanisms associated with EV-miRNAs in vivo and in vitro. **Results:** Under high-glucose conditions, monocyte-derived EVs aggravated EC injury by upregulating miR-191-3p, which targets CYLD and thereby activates the NF-κB pathway. Meanwhile, EC-derived EVs enhanced monocyte inflammation and adhesion by downregulating miR-615-3p, upregulating IFNGR2, and activating the STAT3 pathway. Targeted intervention of these key molecules effectively ameliorated cellular injury in vitro and partially relieved renal damage in vivo. **Conclusions:** This study confirms that EV-miRNA-mediated EC-monocyte crosstalk is involved in the pathogenesis of DKD, and establishes two core regulatory axes: miR-191-3p/CYLD/NF-κB and miR-615-3p/IFNGR2/STAT3. It also reveals an intrinsic link between microcirculatory dysfunction and immune injury in DKD, while the potential of these miRNAs as diagnostic biomarkers and therapeutic targets still remains to be further validated. **Keywords:** Diabetic kidney disease; Endothelial cells; Monocytes; miR-191-3p; miR-615-3p. Copyright © 2026 Elsevier B.V. All rights reserved. [PubMed Disclaimer](https://pubmed.ncbi.nlm.nih.gov/disclaimer/) ## Conflict of interest statement Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. ## Similar articles * [ Small extracellular vesicles-shuttled miR-23a-3p from mesenchymal stem cells alleviate renal fibrosis and inflammation by inhibiting KLF3/STAT3 axis in diabetic kidney disease. ](https://pubmed.ncbi.nlm.nih.gov/39018690/) Li Q, Liu J, Su R, Zhen J, Liu X, Liu G.Li Q, et al.Int Immunopharmacol. 2024 Sep 30;139:112667. doi: 10.1016/j.intimp.2024.112667. Epub 2024 Jul 16.Int Immunopharmacol. 2024.PMID: 39018690 * [ SIV Infection Regulates Compartmentalization of Circulating Blood Plasma miRNAs within Extracellular Vesicles (EVs) and Extracellular Condensates (ECs) and Decreases EV-Associated miRNA-128. ](https://pubmed.ncbi.nlm.nih.gov/36992331/) Kopcho S, McDew-White M, Naushad W, Mohan M, Okeoma CM.Kopcho S, et al.Viruses. 2023 Feb 24;15(3):622. doi: 10.3390/v15030622.Viruses. 2023.PMID: 36992331Free PMC article. * [ MicroRNA-370-3p shuttled by breast cancer cell-derived extracellular vesicles induces fibroblast activation through the CYLD/Nf-κB axis to promote breast cancer progression. ](https://pubmed.ncbi.nlm.nih.gov/33629796/) Ren Z, Lv M, Yu Q, Bao J, Lou K, Li X.Ren Z, et al.FASEB J. 2021 Mar;35(3):e21383. doi: 10.1096/fj.202001430RR.FASEB J. 2021.PMID: 33629796 * [ Extracellular vesicles derived from mesenchymal stem cells alleviate renal fibrosis via the miR-99b-5p/mTOR/autophagy axis in diabetic kidney disease. ](https://pubmed.ncbi.nlm.nih.gov/40103007/) Li R, Tao H, Pan K, Li R, Guo Z, Chen X, Li Z.Li R, et al.Stem Cell Res Ther. 2025 Mar 18;16(1):142. doi: 10.1186/s13287-025-04265-x.Stem Cell Res Ther. 2025.PMID: 40103007Free PMC article. * [ Extracellular Vesicle-Derived MicroRNAs as Early Diagnostic Biomarkers of Diabetic Nephropathy and Cardiovascular Diseases in Type 2 Diabetes. ](https://pubmed.ncbi.nlm.nih.gov/42353293/) Arailym Y, Abaildayev A, Ayaz B.Arailym Y, et al.Int J Mol Sci. 2026 Jun 20;27(12):5581. doi: 10.3390/ijms27125581.Int J Mol Sci. 2026.PMID: 42353293Free PMC article.Review. 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