bims-engexo Biomed News
on Engineered exosomes
Issue of 2025–02–02
thirteen papers selected by
Ravindran Jaganathan, Universiti Kuala Lumpur
  1. Exosome-mediated CRISPR/Cas delivery: A cutting-edge frontier in cancer gene therapy.
  2. Roles for Exosomes in the Pathogenesis, Drug Delivery and Therapy of Psoriasis.
  3. Resveratrol loaded microglia-derived exosomes attenuate astrogliasis by restoring mitochondrial function to reduce spinal cord injury.
  4. Follicular fluid-derived exosomes rejuvenate ovarian aging through miR-320a-3p-mediated FOXQ1 inhibition.
  5. An Integrating Microfluidic System for Concentration Gradient Generation of Exosomes and Exosome-Assisted Single-Cell-Derived Tumor-Sphere Formation.
  6. Mannose-modified exosomes loaded with MiR-23b-3p target alveolar macrophages to alleviate acute lung injury in Sepsis.
  7. Biology of extracellular vesicles and the potential of tumor-derived vesicles for subverting immunotherapy of cancer.
  8. Cell Membrane-Integrated Neuroligin-1 Regulates the Anti-Inflammatory Effects of CRC Cell-Derived Exosomes.
  9. Platelet membrane-modified exosomes targeting plaques to activate autophagy in vascular smooth muscle cells for atherosclerotic therapy.
  10. Stem cell-derived exosome delivery systems for treating atherosclerosis: The new frontier of stem cell therapy.
  11. Regulatory Immune Cell-derived Exosomes: Modes of Action and Therapeutic Potential in Transplantation.
  12. CircPRKD3-loaded exosomes concomitantly elicit tumor growth inhibition and glioblastoma microenvironment remodeling via inhibiting STAT3 signaling.
  13. MiR-186-5p carried by M2 macrophage-derived exosomes downregulates TRPP2 expression in airway smooth muscle to alleviate asthma progression.
  1. Gene. 2025 Jan 28. pii: S0378-1119(25)00084-8. [Epub ahead of print] 149296
    Exosome-mediated CRISPR/Cas delivery: A cutting-edge frontier in cancer gene therapy.
    Bhavanisha Rithiga S, Rajib Dhar, Arikketh Devi.
      Cancer is considered the second most common disease globally. In the past few decades, many approaches have been proposed for cancer treatment. One among those is targeted therapy using CRISPR-Cas system which plays an irreplaceable role in translational research through gene editing. However, due to its inability to cope with specific targeting, off-target effects, and limited tumor penetration, it is very challenging to use this approach in cancer studies. To increase its efficacy, CRISPR components are engineered into the extracellular vesicles (EVs), especially exosomes (a subpopulation of EVs). Exosomes have a significant role in cellular communication. Exosome-based CRISPR-Cas system transport for gene editing enhanced specificity, reduced off-target effects, and improved therapeutic potential. In this review, we highlighted the role of exosomes and the CRISPR-Cas system in cancer research, exosome-based CRISPR delivery for cancer treatment, and its future orientation.
    Keywords:  CRISPR/Cas; Cancer; Exosomes; Therapeutic potential
    DOI:  https://doi.org/10.1016/j.gene.2025.149296
  2. Pharmaceutics. 2025 Jan 02. pii: 51. [Epub ahead of print]17(1):
    Roles for Exosomes in the Pathogenesis, Drug Delivery and Therapy of Psoriasis.
    Yuchao Chen, Huazhen Liu, Yuming He, Bin Yang, Weihui Lu, Zhenhua Dai.
      Psoriasis is a chronic, recurrent and inflammatory skin disease. Although conventional immunosuppressants can ameliorate psoriatic symptoms, it tends to relapse over time. Previous studies have shown that exosomes from both immune and non-immune cells participate in psoriatic immunopathology. The biologically active cargoes in exosomes accelerate psoriasis progression by altering gene profiles and signaling pathways of neighboring cells. On the other hand, exosomes can be utilized as drug delivery platforms for psoriasis treatment. Especially, engineered exosomes may serve as drug delivery systems for effective delivery of proteins, nucleic acids or other drugs due to their low immunogenicity, good stability and ability to fuse with target cells. Therefore, investigation into the mechanisms underlying intercellular communications mediated by exosomes in skin lesions likely helps design drugs for therapy of psoriasis. In this review, we have summarized recent advances in the biogenesis of exosomes and their potential roles in the pathogenesis and treatment of psoriasis and further discussed their challenges and future directions in psoriasis treatment. In particular, this review highlights the immunoregulatory function of exosomes derived from immune or non-immune cells and exosome-based therapeutic applications in psoriasis, including their drug delivery systems. Thus, this review may help accelerate applications of exosomes for drug delivery and treatment of psoriasis.
    Keywords:  drug delivery; exosomes; immunoregulation; molecular biology; psoriasis
    DOI:  https://doi.org/10.3390/pharmaceutics17010051
  3. Chem Biol Interact. 2025 Jan 28. pii: S0009-2797(25)00037-7. [Epub ahead of print] 111407
    Resveratrol loaded microglia-derived exosomes attenuate astrogliasis by restoring mitochondrial function to reduce spinal cord injury.
    Jingwen Cui, Sen Lin, Mingyuan Zhang.
      The activation of astrocytes in the injured lesion induces the progression of spinal cord injury (SCI). However, adverse side-effects during systemic administration have limited applications. Exosomes (Exos) are an emerging clinical treatment method that exerts anti-inflammatory effects by reducing pro-inflammatory factors and promoting functional recovery. Exosomes exhibit great potential as carriers of traditional Chinese medicine, attributed to their high delivery efficiency to internalized and targeted accumulation in inflammatory tissues. Herein, We synthesized resveratrol loaded microglia-derived exosomes (R-MDEs) for highly efficient accumulation and infiltration in the injured spinal cord. In vitro and in vivo experiments suggested that R-MDEs effectively accumulated in A1 astrocytes, inhibited reactive oxygen species (ROS) and glial scar formation by reprogramming the metabolic astrocytes. R-MDEs achieve a synergistic therapeutic effect of immunomodulation and neuroprotection, thereby shedding new light on the application of Exos and provides great potential for SCI.
    Keywords:  Astrocytes; Exosomes; Inflammation; Reactive oxygen species; Resveratrol; Spinal cord injury
    DOI:  https://doi.org/10.1016/j.cbi.2025.111407
  4. Life Med. 2024 Feb;3(1): lnae013
    Follicular fluid-derived exosomes rejuvenate ovarian aging through miR-320a-3p-mediated FOXQ1 inhibition.
    Yu Liu, Hongbei Mu, Yu Chen, Kexin Li, Qiaojuan Mei, Lingjuan Wang, Tianyu Tang, Qiuzi Shen, Huaibiao Li, Ling Zhang, Jing Li, Wenpei Xiang.
      Ovarian aging is mainly characterized by a progressive decline in oocyte quantity and quality, which ultimately leads to female infertility. Various therapies have been established to cope with ovarian aging, among which exosome-based therapy is considered a promising strategy that can benefit ovarian functions via multiple pathways. Here, we isolated and characterized exosomes derived from ovarian follicular fluid and profiled the differential expression patterns of noncoding exosomal RNAs in young and aged women. Treatment with young mouse-derived exosomes efficiently rescued ovarian function in aged mice. The follicular fluid exosomes from young mice and miR-320-3p can also promote the proliferation of ovarian granulosa cells and improve mitochondrial function from old mice in vitro. The mechanism may be involve that exosomes transfer miR-320-3p to granulosa cells, and inhibit the expression of FOXQ1. Exosomes also can increase the number of primordial and growing follicles, and improve the developmental ability of oocytes in the old mice in vivo. And hnRNPA2B1 controls miR-320-3p entry into exosomes. This work provides insights into the antiaging potential of follicular fluid-derived exosomes and the underlying molecular mechanisms, which may facilitate prevention of ovarian aging and an improvement in female fertility.
    Keywords:  exosome; follicular fluid; granulosa cells; miRNAs; ovarian aging
    DOI:  https://doi.org/10.1093/lifemedi/lnae013
  5. ACS Sens. 2025 Jan 27.
    An Integrating Microfluidic System for Concentration Gradient Generation of Exosomes and Exosome-Assisted Single-Cell-Derived Tumor-Sphere Formation.
    Long Pang, Chang Tian, Qirui Wang, Zhaohua Zhao, Bofeng Pan, Zichun Luo, Shuqiang Wu, Xueping Li, Jianglin Fan.
      To enhance exploration on tumor stem-like cells (TSCs) without altering their cellular biological characteristics, researchers advocate for application of single-cell-derived tumor-spheres (STSs). TSCs are regulated by their surrounding microenvironment, making it crucial to simulate a tumor microenvironment to facilitate STS formation. Recently, exosomes that originated from the tumor microenvironment have emerged as a promising approach for mimicking the tumor microenvironment. In the tumor microenvironment, various associated cells (such as fibroblasts, endothelial cells, and immune cells) play crucial roles. Utilizing exosomes derived from these cells enabled us to simulate the tumor microenvironment and promote STS formation. Herein, we have developed an integrated microfluidic platform to generate serial concentration gradients and evaluate the effects of multiple exosomes on STS formation. To demonstrate the feasibility of our approach, we generated serial concentration gradients of exosomes derived from two different cell types (HUVEC and NIH/3T3 cells) and assessed their effects on STS formation. Subsequently, we investigated the drug resistance of STSs treated with free doxorubicin and doxorubicin-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles. Our findings revealed that the serial concentration gradients of mixed exosomes could be successfully generated, leading to an enhanced formation rate and size of STSs. Compared to exosomes derived from one cell type, the mixed exosomes exhibited superior promotion of STS formation. Additionally, nanomedicines demonstrated a reduction in the drug resistance of TSCs compared to free drug treatment, particularly in smaller and/or more deformable TSCs. This platform provides an innovative approach for STS formation enhancement and tumor microenvironment simulation.
    Keywords:  cell mechanical property; exosome-assisted sphere formation; microfluidic chip; nanomedicine; single-cell cultivation; single-cell-derived sphere; tumor stem cells
    DOI:  https://doi.org/10.1021/acssensors.4c01542
  6. J Control Release. 2025 Jan 25. pii: S0168-3659(25)00083-5. [Epub ahead of print]
    Mannose-modified exosomes loaded with MiR-23b-3p target alveolar macrophages to alleviate acute lung injury in Sepsis.
    Jiezhi Lin, Lu Yang, Tianyi Liu, Hui Zhao, Yingying Liu, Futing Shu, Hongchao Huang, Wenzhang Liu, Wei Zhang, Luofeng Jiang, Shichu Xiao, Yongjun Zheng, Zhaofan Xia.
      The anti-inflammatory role of miR-23b-3p (miR-23b) is known in autoimmune diseases like multiple sclerosis, systemic lupus erythematosus, and rheumatoid arthritis. However, its role in sepsis-related acute lung injury (ALI) and its effect on macrophages in ALI remain unexplored. This investigation aimed to evaluate miR-23b's therapeutic potential in macrophages in the context of ALI. The study found reduced miR-23b expression in macrophages within ALI tissue. Intratracheal delivery of miR-23b mimics alleviated ALI by partially inhibiting M1 macrophage activation through the Lpar1-NF-κB pathway. Effective delivery systems are crucial for prolonging miR-23b activity in the lungs, reducing dosage, and minimizing side effects by specifically targeting macrophages. However, current vector systems for nucleic acid delivery, including viral, lipid-based, polymer-based, and peptide-based vectors, face limitations due to eliciting immune responses. Exosomes have garnered significant attention as a leading gene delivery system due to the safety, effectivity and low immunogenicity. We further isolated exosomes from bone marrow-derived mesenchymal stem cells, modified exosomes with mannosylated ligands to enhance the targeted delivery of miR-23b to macrophage. This approach represents a promising novel therapeutic strategy for treating sepsis-induced ALI.
    Keywords:  Acute lung injury; Exosomes; Macrophages; MiR-23b-3p; Sepsis
    DOI:  https://doi.org/10.1016/j.jconrel.2025.01.073
  7. J Immunother Cancer. 2025 Jan 23. pii: e010376. [Epub ahead of print]13(1):
    Biology of extracellular vesicles and the potential of tumor-derived vesicles for subverting immunotherapy of cancer.
    Theresa L Whiteside.
      Extracellular vesicles (EVs) are produced by all living cells and are present in all body fluids. EVs are heterogeneous in size, biogenesis, molecular/genetic content and functions. They constitute a part of the intercellular communication system. Among them, a subset of small EVs (sEVs) (30-150 nm) originating in the tumor cell endosomes and often referred to as "tumor cell-derived exosomes" have been of special interest. Tumors have adapted sEV they produce to promoting their own survival. Plasma of patients with cancer contains variably elevated numbers of tumor-derived sEV called "TEX," which differ from circulating sEV produced by non-malignant cells by the immunosuppressive phenotype and the molecular/genetic content. Immunosuppressive molecular profiles and abilities to signal, enter and functionally reprogram a variety of recipient cells enable TEX to exert pro-tumor effects that promote tumor resistance to immunotherapy. This review describes phenotypic and functional attributes of TEX that underline their reprogramming capabilities. It also considers mechanisms responsible for TEX pro-tumor activities and the potential significance of TEX signaling for responses of patients with cancer to immune therapies.
    Keywords:  Cytokine; Immunocompromised; Immunosuppression; Immunotherapy; Tumor microenvironment - TME
    DOI:  https://doi.org/10.1136/jitc-2024-010376
  8. Int J Mol Sci. 2025 Jan 09. pii: 503. [Epub ahead of print]26(2):
    Cell Membrane-Integrated Neuroligin-1 Regulates the Anti-Inflammatory Effects of CRC Cell-Derived Exosomes.
    Mohammad Mahmoudian, Francesco Trotta, Stefania Raimondo, Federico Bussolino, Marco Arese.
      Tumor-associated macrophages (TAMs) are one of the most abundant cell types in the colorectal cancer (CRC) tumor microenvironment (TME). CRC cell-derived exosomes support macrophage polarization toward an M2-like phenotype, which leads to tumor growth and metastasis. Neuroligin 1 (NLG1) is a transmembrane protein critical in synaptic function. We reported that NLG1 via an autocrine manner promotes CRC progression by modulating the APC/β-catenin pathway. This study aimed to answer whether NLG1 is involved in the exosome-mediated intercellular cross-talk between CRC and TAMs. Our results showed that exosomes of NLG1-expressing CRC cells induce M2-like (CD206high CD80low) polarization in macrophages. On the other hand, we found that the exosomes of the NLG1 knocked-down CRC cells reinforce the expression of CD80 and pro-inflammatory genes, including IL8, IL1β, and TNFα, in the macrophages, indicating an M1-like phenotype polarization. In conclusion, NLG1, as a cell-membrane-integrated protein, could be a therapeutic target on the surface of the CRC cells for developing clinical treatments to inhibit exosome-induced anti-inflammatory immune responses in TME.
    Keywords:  Neuroligin-1; colorectal cancer cells; exosome; macrophages
    DOI:  https://doi.org/10.3390/ijms26020503
  9. Drug Deliv Transl Res. 2025 Jan 28.
    Platelet membrane-modified exosomes targeting plaques to activate autophagy in vascular smooth muscle cells for atherosclerotic therapy.
    Yu Jiang, Zhi-Yao Wei, Zhi-Feng Song, Miao Yu, Ji Huang, Hai-Yan Qian.
      Atherosclerosis is one of the leading causes of ischemic cardiovascular disease worldwide. Recent studies indicated that vascular smooth muscle cells (VSMCs) play an indispensable role in the progression of atherosclerosis. Exosomes derived from mesenchymal stem cells (MSCs) have demonstrated promising clinical applications in the treatment of atherosclerosis. However, there are still challenges and limitations persist in targeted therapy. This study aims to develop a bionic nano-delivery system by fusing platelet membranes with exosomes (MSC-ExoP) and explore the anti-atherosclerosis effect of MSC-ExoP by improving the targeting efficiency and participating in regulating the pathophysiological processes associated with VSMCs. The morphology, particle size, stability, and fusion efficiency of MSC-ExoP were assessed using transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), immunofluorescence staining, and Western blotting, respectively. MSC-ExoP was administered intravenously into ApoE-/- mice via the tail vein. In vivo, immunofluorescence staining was used to assess the targeting efficacy of MSC-ExoP. The ORO staining, H&E staining, Masson staining, aortic root immunofluorescence staining, and Western blot were utilized to evaluate the VSMC autophagy and anti-atherosclerosis effects of MSC-ExoP. In vitro, the autophagy activation of MSC-ExoP on VSMCs was further assessed by immunofluorescence staining and Western blotting. The effects of MSC-ExoP on VSMCs proliferation, migration, and foam cell formation were detected by EdU experiment, Transwell experiment, wound healing experiment, ORO staining, and BODIPY staining. The TEM revealed that MSC-ExoP retained a ring nanostructure, which was similar to MSC-Exo in morphology. NTA analysis indicated the MSC-ExoP exhibited a slight increase after cell membrane fusion. Besides, the stability analysis of exosomes and MSC-ExoP resulted in no significant changes in particle size. Western blot analysis confirmed that MSC-ExoP simultaneously expressed platelet-specific markers (GPVI, GPIbα, CD62P) and exosome-specific markers (CD81, TSG101, and Alix). In ApoE-/- mice, the immunofluorescence of aorta and its roots was significantly enhanced after injection of DiI-labeled MSC-ExoP, indicating enhanced targeting of MSC-Exo to atherosclerotic plaques by platelets. In vivo experiments demonstrated that MSC-ExoP could significantly suppress the progression of atherosclerosis and reduce the area of atherosclerotic plaques by reducing lipid deposition and necrotic nucleus area and increasing collagen content. In vitro experiments further revealed that the uptake of MSC-ExoP by foam cells significantly increased, and their proliferation, migration, and foam formation were inhibited by autophagy activation. This study demonstrated successful fusion of platelet membranes with exosomes derived from MSCs. MSC-ExoP could significantly improve the targeting efficiency of atherosclerosis and play an anti-atherosclerosis effect by activating VSMC autophagy.
    Keywords:  Atherosclerosis; Autophagy; Exosome; Targeting delivery; Vascular smooth muscle cells
    DOI:  https://doi.org/10.1007/s13346-025-01792-1
  10. Mater Today Bio. 2025 Feb;30 101440
    Stem cell-derived exosome delivery systems for treating atherosclerosis: The new frontier of stem cell therapy.
    Hassan Tariq, Syeda Zunaira Bukhari, Ruibing An, Jian Dong, Ayesha Ihsan, Muhammad Rizwan Younis.
      Cardiovascular diseases (CVDs) are a leading cause of mortality worldwide. As a chronic inflammatory disease with a complicated pathophysiology marked by abnormal lipid metabolism and arterial plaque formation, atherosclerosis is a major contributor to CVDs and can induce abrupt cardiac events. The discovery of exosomes' role in intercellular communication has sparked a great deal of interest in them recently. Exosomes are involved in strategic phases of the onset and development of atherosclerosis because they have been identified to control pathophysiologic pathways including inflammation, angiogenesis, or senescence. This review investigates the potential role of stem cell-derived exosomes in atherosclerosis management. We briefly introduced atherosclerosis and stem cell therapy including stem cell-derived exosomes. The biogenesis of exosomes along with their secretion and isolation have been elaborated. The design engineering of exosomes has been summarized to present how drug loading and surface modification with targeting ligands can improve the therapeutic and targeting capacity of exosomes, demonstrating atheroprotective action. Moreover, the mechanism of action (endothelial dysfunction, reduction of dyslipidemia, macrophage polarization, vascular calcification, and angiogenesis) of drug-loaded exosomes to treat atherosclerosis has been discussed in detail. In the end, a comparative and balanced viewpoint has been given regarding the current challenges and potential solutions to advance exosome engineering for cardiovascular therapeutic applications.
    DOI:  https://doi.org/10.1016/j.mtbio.2024.101440
  11. Transplantation. 2025 Jan 27.
    Regulatory Immune Cell-derived Exosomes: Modes of Action and Therapeutic Potential in Transplantation.
    Cindy G Avalos-de Leon, Angus W Thomson.
      Reduced dependence on antirejection agents, improved long-term allograft survival, and induction of operational tolerance remain major unmet needs in organ transplantation due to the limitations of current immunosuppressive therapies. To address this challenge, investigators are exploring the therapeutic potential of adoptively transferred host- or donor-derived regulatory immune cells. Extracellular vesicles of endosomal origin (exosomes) secreted by these cells seem to be important contributors to their immunoregulatory properties. Twenty years ago, it was first reported that donor-derived exosomes could extend the survival of transplanted organs in rodents. Recent studies have revealed that regulatory immune cells, such as regulatory myeloid cells (dendritic cells, macrophages, or myeloid-derived suppressor cells), regulatory T cells, or mesenchymal stem/stromal cells can suppress graft rejection via exosomes that express a cargo of immunosuppressive molecules. These include cell surface molecules that interact with adaptive immune cell receptors, immunoregulatory enzymes, and micro- and long noncoding RNAs that can regulate inflammatory gene expression via posttranscriptional changes and promote tolerance through promotion of regulatory T cells. This overview analyzes the diverse molecules and mechanisms that enable regulatory immune cell-derived exosomes to modulate alloimmunity and promote experimental transplant tolerance. We also discuss the potential benefits and limitations of their application as therapeutic entities in organ transplantation.
    DOI:  https://doi.org/10.1097/TP.0000000000005309
  12. Neuro Oncol. 2025 Jan 27. pii: noaf019. [Epub ahead of print]
    CircPRKD3-loaded exosomes concomitantly elicit tumor growth inhibition and glioblastoma microenvironment remodeling via inhibiting STAT3 signaling.
    Xiaoming Zhang, Mengyuan Jiang, Wanxiang Niu, Ben Xu, Ce Zhang, Minglong Yang, Shanshan Hu, Chaoshi Niu.
       BACKGROUND: Glioblastoma stem cells (GSCs) and their exosomes (exos) are involved in shaping the immune microenvironment, which is important for tumor invasion and recurrence. However, studies involving GSC-derived exosomal circular RNAs (GDE-circRNAs) in regulating tumor microenvironment (TME) remain unknown. Here, we comprehensively evaluated the significance of a novel immune-related GDE-circRNA in glioma microenvironment.
    METHODS: GDE-circPRKD3 was screened out through high-throughput sequencing and verified by RT-PCR, sanger sequencing and RNase R assays. A series of in vitro and in vivo experiments were performed to investigate the function of GDE-circPRKD3. RNA-seq, RNA immunoprecipitation, multicolor flow cytometry and western blotting were used to explore the regulation of GDE-circPRKD3 on STAT3 signaling-mediated TME remodeling.
    RESULTS: We have characterized a circRNA PRKD3 in GSC exosomes, and lower circPRKD3 expression predicts a worse prognosis for glioblastoma patients. Overexpression of GDE-circPRKD3 significantly impairs the biological competence of glioma and prolongs the survival of xenograft mice. GDE-circPRKD3 binds to HNRNPC in an m6A-dependent manner, accelerates mRNA decay of IL6ST and inhibits downstream target STAT3. Notably, GDE-circPRKD3 promotes CXCL10 secretion by reprogramming tumor-associated macrophages, which in turn recruits CD8+ tumor infiltrating lymphocytes against GBM. Moreover, brain-targeted lipid nanoparticle delivery of circPRKD3 combined with immune checkpoint blockade therapy achieves significant combinatorial benefits.
    CONCLUSION: This study provides a novel mechanism by which GDE-circPRKD3 relies on STAT3 signaling to remodel immunosuppressive TME and offers a potential RNA immunotherapy strategy for GBM treatment.
    Keywords:  STAT3; circPRKD3; exosome; glioma stem cell; tumor microenvironment
    DOI:  https://doi.org/10.1093/neuonc/noaf019
  13. Int Immunopharmacol. 2025 Jan 29. pii: S1567-5769(25)00096-7. [Epub ahead of print]148 114107
    MiR-186-5p carried by M2 macrophage-derived exosomes downregulates TRPP2 expression in airway smooth muscle to alleviate asthma progression.
    Zunyun Wang, Yan Ren, Yicong Li, Yuxin Zhang, Suwen Bai, Wenxuan Hou, Wenjun Zhang, Yanheng Yao, Hongxian Zhao, Minghua Wang, Yumei Luo, Gang Pang, Juan Du.
      Bronchial asthma (asthma) is a chronic inflammatory disease of the airways that remains an unresolved problem. Reportedly M2 macrophages and exosomes play a role in inflammation, including asthma. We investigated the roles of M2 macrophage-derived exosomes (M2-Exos) effect in asthmatic progression by using ovalbumin (OVA) induced asthmatic mice model. M2-Exos significantly ameliorated the pulmonary inflammatory response and airway hyperresponsiveness in asthmatic mice and suppressed aberrant proliferation and transient receptor potential polycystic protein 2(TRPP2) expression in LPS-stimulated primary airway smooth muscle cells (ASMCs). Then, we found that miR-186-5p of M2-Exos could target TRPP2 through online database analysis. However, miR-186-5p downregulation by miR-186-5p inhibitors decreased the protective effect of M2-Exos in asthmatic mouse and cellular models. miR-186-5p was identified and selectively combined with the polycystin-2 gene encoding TRPP2 protein, inhibited TRPP2 protein production, and downregulated TRPP2 expression. A reduction in the number of TRPP2 calcium (Ca) channels formed on the cell membrane leads to a decreased intracellular Ca2+ concentration ([Ca2+] i), causing reduced ASMC contraction and proliferation, thereby improving airway hyperresponsiveness and airway remodeling in asthma. Collectively, we conclude that M2 exosomal miR-186-5p to alleviate asthma progression and airway hyperresponsiveness though downregulating TRPP2 expression. These results may offer a novel insight to the treatment and drug delivery of asthma.
    Keywords:  Asthma; Exosomes; M2 macrophages; MiR-186-5p; Transient receptor potential polycystic protein 2
    DOI:  https://doi.org/10.1016/j.intimp.2025.114107
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