Macrophage-derived, LRG1-enriched extracellular vesicles exacerbate aristolochic acid nephropathy in a TGFβR1-dependent manner

Jiang, Wenjuan; Chen, Xu; Xu, Songbing; Wan, Shouhong; Du, Changlin; Dong, Jiahui; Feng, Rui; Huang, Cheng; Li, Jun; Ma, Tran

doi:10.1007/s10565-021-09666-1

Cited by 14 publications

(9 citation statements)

References 33 publications

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“…In conditions of altered homeostasis that typically accompany disease, transcription of the Lrg1 gene has been reported to be highly upregulated in endothelial cells [ 4 , 70 , 73 – 75 ], several types of epithelial cells [ 15 , 17 , 26 , 28 , 68 , 76 ], fibroblasts [ 34 , 57 , 70 , 77 ] and myeloid cells [ 11 , 56 , 72 , 78 – 81 ] including microglia [ 82 ] (Fig. 5 ).…”

Section: Reviewmentioning

confidence: 99%

LRG1: an emerging player in disease pathogenesis

et al. 2022

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The secreted glycoprotein leucine-rich α-2 glycoprotein 1 (LRG1) was first described as a key player in pathogenic ocular neovascularization almost a decade ago. Since then, an increasing number of publications have reported the involvement of LRG1 in multiple human conditions including cancer, diabetes, cardiovascular disease, neurological disease, and inflammatory disorders. The purpose of this review is to provide, for the first time, a comprehensive overview of the LRG1 literature considering its role in health and disease. Although LRG1 is constitutively expressed by hepatocytes and neutrophils, Lrg1−/− mice show no overt phenotypic abnormality suggesting that LRG1 is essentially redundant in development and homeostasis. However, emerging data are challenging this view by suggesting a novel role for LRG1 in innate immunity and preservation of tissue integrity. While our understanding of beneficial LRG1 functions in physiology remains limited, a consistent body of evidence shows that, in response to various inflammatory stimuli, LRG1 expression is induced and directly contributes to disease pathogenesis. Its potential role as a biomarker for the diagnosis, prognosis and monitoring of multiple conditions is widely discussed while dissecting the mechanisms underlying LRG1 pathogenic functions. Emphasis is given to the role that LRG1 plays as a vasculopathic factor where it disrupts the cellular interactions normally required for the formation and maintenance of mature vessels, thereby indirectly contributing to the establishment of a highly hypoxic and immunosuppressive microenvironment. In addition, LRG1 has also been reported to affect other cell types (including epithelial, immune, mesenchymal and cancer cells) mostly by modulating the TGFβ signalling pathway in a context-dependent manner. Crucially, animal studies have shown that LRG1 inhibition, through gene deletion or a function-blocking antibody, is sufficient to attenuate disease progression. In view of this, and taking into consideration its role as an upstream modifier of TGFβ signalling, LRG1 is suggested as a potentially important therapeutic target. While further investigations are needed to fill gaps in our current understanding of LRG1 function, the studies reviewed here confirm LRG1 as a pleiotropic and pathogenic signalling molecule providing a strong rationale for its use in the clinic as a biomarker and therapeutic target.

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Section: Reviewmentioning

confidence: 99%

LRG1: an emerging player in disease pathogenesis

et al. 2022

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“…Exosomes are stable, so it can improve the half-life of drugs in the process of blood circulation. e special lipid composition of exosomes stimulated the fusion between exosomes and target cells and also enhanced the cell-cell communication [22,23]. ere were many studies on the functions of exosomes for delivering gene drugs for the treatment of tumors [24].…”

Section: Discussionmentioning

confidence: 99%

Engineered Exosomes Loaded with miR-563 Inhibit Lung Cancer Growth

Gao

Yang

Yin

et al. 2022

Journal of Oncology

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The malignancy of lung cancer (LC) is serious in the world. Exosomes are well-known natural nanovesicles, which are reported to have the potential to carry functional miRNAs as natural carriers and deliver chemotherapeutic drugs. However, the safety and functions of the engineered exosomes for delivering miRNA for the treatment of LC remain to be evaluated. In this study, we found that miR-563 is related to lung cancer from GeneCard database. RT-qPCR and in situ hybridization (ISH) were used to assess miR-563 expression in clinical samples. We prepared and verified the engineered exosomes loaded with miR-563 both in vitro and in vivo. In vitro, flow cytometry, Western blot, and other experimental methods were performed to evaluate the antitumor effect of miR-563 loaded exosomes. In in vivo, the LC mouse model was used to observe the effect of the prepared exosomes. The safety of using this exosomes was accessed by liver function test, hematological analysis, and H&E staining in major organs of the mice. Our findings indicated that the miR-563 loaded engineered exosomes inhibit the A549 cells growth in vitro, by inhibiting the tumor cell proliferation, migration, and invasion and promoting apoptosis. In in vivo, these engineered exosomes were enriched in tumor tissue after injecting to LC model mice and impacted tumor tissue by inhibiting the tumor volume and tumor weight. Importantly, our study indicated that miR-563 loaded engineered exosomes have the potential for clinical application for LC treatment with acceptable safety profiles. Our findings indicate a novel potential therapeutic target for lung cancer patients by miR-563 loaded engineered exosomes.

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“…Macrophage-derived EVs play a crucial role in intercellular signaling to renal tubular cells. Although EVs from macrophages isolated from diseased kidneys worsened the condition when reintroduced into the same animals, healthy macrophage-derived EVs have shown potential as nanocarriers for therapeutic agents (C. Guo et al, 2023;W. Jiang et al, 2022;.…”

Section: Extracellular Vesicles For Renal Disease Treatmentmentioning

confidence: 99%

“…Macrophage‐derived EVs play a crucial role in intercellular signaling to renal tubular cells. Although EVs from macrophages isolated from diseased kidneys worsened the condition when reintroduced into the same animals, healthy macrophage‐derived EVs have shown potential as nanocarriers for therapeutic agents (C. Guo et al, 2023; W. Jiang et al, 2022; Y. Liu et al, 2023; Z. Zhang et al, 2022). Tang et al demonstrated the efficacy of dexamethasone‐loaded EVs from mouse macrophage RAW 264.7 cells in mitigating LPS‐induced AKI and Adriamycin‐induced glomerular damage (Tang et al, 2019).…”

Section: Extracellular Vesicles For Renal Disease Treatmentmentioning

confidence: 99%

A quantitative review of nanotechnology‐based therapeutics for kidney diseases

Cheng,

Ngoc Ta,

Hsia

et al. 2024

WIREs Nanomed Nanobiotechnol

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Kidney‐specific nanocarriers offer a targeted approach to enhance therapeutic efficacy and reduce off‐target effects in renal treatments. The nanocarriers can achieve organ or cell specificity via passive targeting and active targeting mechanisms. Passive targeting capitalizes on the unique physiological traits of the kidney, with factors like particle size, charge, shape, and material properties enhancing organ specificity. Active targeting, on the other hand, achieves renal specificity through ligand‐receptor interactions, modifying nanocarriers with molecules, peptides, or antibodies for receptor‐mediated delivery. Nanotechnology‐enabled therapy targets diseased kidney tissue by modulating podocytes and immune cells to reduce inflammation and enhance tissue repair, or by inhibiting myofibroblast differentiation to mitigate renal fibrosis. This review summarizes the current reports of the drug delivery systems that have been tested in vivo, identifies the nanocarriers that may preferentially accumulate in the kidney, and quantitatively compares the efficacy of various cargo‐carrier combinations to outline optimal strategies and future research directions.This article is categorized under: Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Therapeutic Approaches and Drug Discovery > Emerging Technologies

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Macrophage-derived, LRG1-enriched extracellular vesicles exacerbate aristolochic acid nephropathy in a TGFβR1-dependent manner

Cited by 14 publications

References 33 publications

LRG1: an emerging player in disease pathogenesis

LRG1: an emerging player in disease pathogenesis

Engineered Exosomes Loaded with miR-563 Inhibit Lung Cancer Growth

A quantitative review of nanotechnology‐based therapeutics for kidney diseases

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