Efferocytosis fuels malignant pleural effusion through TIMP1

Zhao, Lilan; Giannou, Anastasios D.; Yang, Xu; Shiri, Ahmad Mustafa; Steglich, Babett; Bedke, Tanja; Zhang, Tao; Lücke, Jöran; Scognamiglio, Pasquale; Kempski, Jan; Woestemeier, Anna; Chen, Jing; Agalioti, Theodora; Zazara, Dimitra E.; Lindner, Diana; Janning, Melanie; Hennigs, Jan K.; Jagirdar, Rajesh; Kotsiou, Ourania S.; Zarogiannis, Sotirios G.; Kobayashi, Yasushi; Izbicki, J. R.; Ghosh, Sourav; Rothlin, Carla V.; Bosurgi, Lidia; Huber, Samuel; Gagliani, Nicola

doi:10.1126/sciadv.abd6734

Cited by 7 publications

(9 citation statements)

References 81 publications

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“…Some signalling pathways including TGF‐β2 could modulate ECM formation in multiple organs, such as the eye, liver and lungs 37–39 . Therefore, TGF‐β2 is used to design fibrosis models in vivo, including glaucoma and liver fibrosis 40–42 . Studies have shown that TGF‐β2 could contribute to ECM deposition and inhibit ECM transformation in the AH or trabecular meshwork of glaucoma patients.…”

Section: Discussionmentioning

confidence: 99%

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Low expression of TGF‐β2 and matrilin2 in human aqueous humour with acute primary angle closure

Wang,

Xu,

Hong

et al. 2024

J Cellular Molecular Medi

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Primary angle‐closure glaucoma (PACG) is the leading cause of irreversible blindness in the world. Angle closure induced by pupil block and secondary iris synechia is the fundamental pathology of the PACG. The molecular mechanisms of angle closure have not yet been clearly illustrated. This study was designed to investigate the protein difference in the aqueous humour and explore new biomarker of the PACG. Aqueous humour (AH) was collected from patients with acute primary angle closure (APAC) and cataract (n = 10 in APAC group) and patients with cataract only (n = 10 in control group). Samples were pooled and measured using label‐free proteome technology. Then, the differentially expressed proteins (DEPs) were verified by ELISA using independent AH samples (n = 20 each group). More than 400 proteins were revealed in both groups through proteomics. Comparing the two groups, there were 91DEPs. These proteins participate in biological activities such as inflammation, fibrosis, nerve growth and degeneration and metabolism. We found that the expression of transforming growth factor‐β2 and matrilin2 was downregulated in the APAC group. The two proteins are related to inflammation and extracellular matrix formation, which might be involved in angle closure. This study characterized DEPs in AH of the APAC and found a downregulated protein matrilin2.

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Section: Discussionmentioning

confidence: 99%

“…[37][38][39] Therefore, TGF-β2 is used to design fibrosis models in vivo, including glaucoma and liver fibrosis. [40][41][42] Studies have…”

Section: Matn2mentioning

confidence: 99%

Low expression of TGF‐β2 and matrilin2 in human aqueous humour with acute primary angle closure

Wang,

Xu,

Hong

et al. 2024

J Cellular Molecular Medi

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“…TIMP1 is a secretory glycoprotein that inhibits MMPs, a group of conserved peptidases that degrade ECM proteins 60 . TIMP1 also inhibits cell apoptosis 61 , promotes cell proliferation 62 , and benefits bone health 63 .…”

Section: Discussionmentioning

confidence: 99%

Extracellular vesicles from human urine-derived stem cells delay aging through the transfer of PLAU and TIMP1

Rao,

He,

Wang

et al. 2024

Acta Pharmaceutica Sinica B

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“…TIMP1 augmented macrophage migration and its transformation to M2 type ( 45 ). Reversely, IL10 induces dendritic cells to produce TIMP1 ( 46 ). Furthermore, anti-inflammatory M2-type macrophages down-regulate the expression of VCAM1 in endothelial cells ( 47 ).…”

Section: Discussionmentioning

confidence: 99%

Diagnostic model constructed by five EMT-related genes for renal fibrosis and reflecting the condition of immune-related cells

Guo

Yuan

et al. 2023

Front. Immunol.

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BackgroundRenal fibrosis is a physiological and pathological characteristic of chronic kidney disease (CKD) to end-stage renal disease. Since renal biopsy is the gold standard for evaluating renal fibrosis, there is an urgent need for additional non-invasive diagnostic biomarkers.MethodsWe used R package “limma” to screen out differently expressed genes (DEGs) based on Epithelial-mesenchymal transformation (EMT), and carried out the protein interaction network and GO, KEGG enrichment analysis of DEGs. Secondly, the least absolute shrinkage and selection operator (LASSO), random forest tree (RF), and support vector machine-recursive feature elimination (SVM-RFE) algorithms were used to identify candidate diagnostic genes. ROC curves were plotted to evaluate the clinical diagnostic value of these genes. In addition, mRNA expression levels of candidate diagnostic genes were analyzed in control samples and renal fibrosis samples. CIBERSORT algorithm was used to evaluate immune cells level. Additionally, gene set enrichment analysis (GSEA) and drug sensitivity were conducted.ResultsAfter obtaining a total of 24 DEGs, we discovered that they were mostly involved in several immunological and inflammatory pathways, including NF-KappaB signaling, AGE-RAGE signaling, and TNF signaling. Five genes (COL4A2, CXCL1, TIMP1, VCAM1, and VEGFA) were subsequently identified as biomarkers for renal fibrosis through machine learning, and their expression levels were confirmed by validation cohort data sets and in vitro RT-qPCR experiment. The AUC values of these five genes demonstrated significant clinical diagnostic value in both the training and validation sets. After that, CIBERSORT analysis showed that these biomarkers were strongly associated with immune cell content in renal fibrosis patients. GSEA also identifies the potential roles of these diagnostic genes. Additionally, diagnostic candidate genes were found to be closely related to drug sensitivity. Finally, a nomogram for diagnosing renal fibrosis was developed.ConclusionCOL4A2, CXCL1, TIMP1, VCAM1, and VEGFA are promising diagnostic biomarkers of tissue and serum for renal fibrosis.

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Efferocytosis fuels malignant pleural effusion through TIMP1

Cited by 7 publications

References 81 publications

Low expression of TGF‐β2 and matrilin2 in human aqueous humour with acute primary angle closure

Low expression of TGF‐β2 and matrilin2 in human aqueous humour with acute primary angle closure

Extracellular vesicles from human urine-derived stem cells delay aging through the transfer of PLAU and TIMP1

Diagnostic model constructed by five EMT-related genes for renal fibrosis and reflecting the condition of immune-related cells

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