LRG1 May Accelerate the Progression of ccRCC via the TGF-<i>β</i> Pathway

Hong, Quan; Wang, Shuqiang; Liu, Shuxin; Chen, Xiangmei; Cai, Guangyan

doi:10.1155/2020/1285068

Cited by 15 publications

(8 citation statements)

References 23 publications

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“…Moreover, LRG1 has been often over-expressed in multiple diseases. 35 , 36 Similarly, our findings demonstrated that LRG1 was highly-expressed in NP cells and tissues upon IDD. Meanwhile, a previous study revealed that LRG1 knockdown enhances osteoblast viability and collagen synthesis, and suppresses osteoblast apoptosis via promotion of the TGF-β1/SMAD signaling pathway in osteoporosis.…”

Section: Discussionsupporting

confidence: 78%

microRNA-129-5p shuttled by mesenchymal stem cell-derived extracellular vesicles alleviates intervertebral disc degeneration via blockade of LRG1-mediated p38 MAPK activation

Cui

Zhang

2021

J Tissue Eng

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Mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) have been reported to deliver exogenous microRNAs (miRNAs or miRs) to reduce the progression of intervertebral disc degeneration (IDD). The purpose of the current study was to investigate the therapeutic potential of MSC-derived EVs delivering miR-129-5p in IDD. First, miR-129-5p expression levels were quantified in nucleus pulposus (NP) tissues of IDD patients. An IL-1β-induced NP cell model with IDD was then established, and co-cultured with EVs derived from MSCs that had been transfected with miR-129-5p mimic or inhibitor to elucidate the effects of miR-129-5p on cell viability, apoptosis, and ECM degradation. In addition, RAW264.7 cells were treated with the conditioned medium (CM) of NP cells. Next, the expression patterns of polarization markers and those of inflammatory factors in macrophages were detected using flow cytometry and ELISA, respectively. Lastly, rat models of IDD were established to validate the in vitro findings. It was found that miR-129-5p was poorly-expressed in NP tissues following IDD. Delivery of miR-129-5p to NP cells by MSC-derived EVs brought about a decrease in NP cell apoptosis, ECM degradation and M1 polarization of macrophages. Moreover, miR-129-5p directly-targeted LRG1, which subsequently promoted the activation of p38 MAPK signaling pathway, thus polarizing macrophages toward the M1 phenotype. Furthermore, MSC-derived EVs transferring miR-129-5p relieved IDD via inhibition of the LRG1/p38 MAPK signaling in vivo. Altogether, our findings indicated that MSC-derived EVs carrying miR-129-5p confer protection against IDD by targeting LRG1 and suppressing the p38 MAPK signaling pathway, offering a novel theranostic marker in IDD.

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Section: Discussionsupporting

confidence: 78%

microRNA-129-5p shuttled by mesenchymal stem cell-derived extracellular vesicles alleviates intervertebral disc degeneration via blockade of LRG1-mediated p38 MAPK activation

Cui

Zhang

2021

J Tissue Eng

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“…Increases with clinical stage [ 12 , 177 , 259 ] Tumour tissue Associated with higher recurrence rate and worse recurrence-free survival [ 256 ] Prostate Serum Elevated in fatal prostate cancer. Positively correlated with high risk of disease progression and mortality [ 260 ] Renal Tumour tissue Overexpressed in clear renal cell carcinoma and negatively related to patient survival [ 261 ] Retinal Tumour tissue Highly expressed in retinoblastoma [ 262 ] List of publications where LRG1 is discussed as a potential biomarker for the diagnosis, prognosis and monitoring of various cancer types. The samples used for LRG1 detection (serum, plasma, tissue section or urine), together with the main findings reported in the studies, are included.…”

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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“…On the other hand, it has been documented that LRG1 can affect leiomyomas through TGF-β signaling. 40,41 Therefore, it is suggested that conducting a series of screenings to assess vitamin D concentration and subsequently maintaining its levels within the appropriate range through the use of vitamin D supplements could significantly contribute to the prevention or treatment of leiomyomas.…”

Section: Discussionmentioning

confidence: 99%

Vitamin D and its binding protein in patients with leiomyomas

Latifi,

Oghbaei,

Salemi

et al. 2024

J of Obstet and Gynaecol

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AimThis study examined the levels of VitD, VitD binding protein (DBP), and free VitD in leiomyomas patients and their association with the quantity, dimensions, and site of fibroid growths. Additionally, we evaluated the potentiality of employing these factors as a biomarker tool for the diagnosis and assessment of uterine fibroid progression.MethodsThis study involved the participation of 55 women with leiomyomas and 50 healthy women. We utilized commercial ELISA kits to measure the levels of total VitD and DBP in their serum. Additionally, we calculated the levels of free VitD and the ratio of VitD to DBP. Moreover, we determined the number, size, and location of the leiomyomas in the patients.ResultsThere were no significant differences in the levels of total VitD between the groups. However, patients had significantly lower levels of free VitD and higher levels of DBP compared to the control group. The size of the largest leiomyomas showed a negative relationship with free VitD and a positive relationship with DBP. Receiver operating characteristic analyses, showed that the cut‐off value for free VitD was 4.47 pg/mL, with a sensitivity of 75.6% and a specificity of 74.4%. The cut‐off value for DBP was 256.2 μg/mL, with a sensitivity of 86% and a specificity of 70.3%.ConclusionsFree VitD and DBP potentially contribute to the development of leiomyomas and are linked to the size of these tumors. The measurement of serum levels of these factors could serve as additional biomarkers for the diagnosis of leiomyomas.

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LRG1 May Accelerate the Progression of ccRCC via the TGF-β Pathway

Cited by 15 publications

References 23 publications

microRNA-129-5p shuttled by mesenchymal stem cell-derived extracellular vesicles alleviates intervertebral disc degeneration via blockade of LRG1-mediated p38 MAPK activation

microRNA-129-5p shuttled by mesenchymal stem cell-derived extracellular vesicles alleviates intervertebral disc degeneration via blockade of LRG1-mediated p38 MAPK activation

LRG1: an emerging player in disease pathogenesis

Vitamin D and its binding protein in patients with leiomyomas

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