Macrophages: versatile players in renal inflammation and fibrosis

Nature Reviews Nephrology, Journal Year: 2019, Volume and Issue: 15(3), P. 144 - 158

Published: Jan. 28, 2019

Language: Английский

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Inflammation and fibrosis

Matrix Biology, Journal Year: 2017, Volume and Issue: 68-69, P. 106 - 121

Published: Nov. 29, 2017

Language: Английский

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WNT–β-catenin signalling — a versatile player in kidney injury and repair

Nature Reviews Nephrology, Journal Year: 2020, Volume and Issue: 17(3), P. 172 - 184

Published: Sept. 28, 2020

Language: Английский

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Crosstalk between hepatic tumor cells and macrophages via Wnt/β-catenin signaling promotes M2-like macrophage polarization and reinforces tumor malignant behaviors

Cell Death and Disease, Journal Year: 2018, Volume and Issue: 9(8)

Published: July 18, 2018

Abstract Tumor-associated macrophages (TAMs) are a major component of tumor microenvironment (TME) and play pivotal roles in the progression hepatocellular carcinoma (HCC). Wnt signaling is evolutionarily conserved participates liver tumorigenesis. Several studies have shown that macrophage-derived ligands can activate cells. However, whether secreted by cells trigger still elusive. In this study, we first verified canonical Wnt/β-catenin was activated during monocyte-to-macrophage differentiation M2-polarized macrophages. Knockdown β-catenin M2 exhibited stronger antitumor characteristics when cocultured with Hepa1-6 HCC series experiments. Activation promoted macrophage polarization through c-Myc. Moreover, co-culturing naïve which secretion blocked knockdown Wntless inhibited vitro. Consistently, growth orthotopically inoculated Wntless-silenced impeded, phenotype M2-like TAMs abrogated due to attenuated TAMs, leading subverted immunosuppressive TME. Finally, confirmed correlation between nuclear accumulation CD68 + human biopsies. Taken together, our study indicates cells-derived stimulate via signaling, results growth, migration, metastasis, immunosuppression HCC. To block Wnts from and/or signal activation may be potential strategy for therapy future.

Language: Английский

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Signaling pathways of chronic kidney diseases, implications for therapeutics

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: June 9, 2022

Abstract Chronic kidney disease (CKD) is a chronic renal dysfunction syndrome that characterized by nephron loss, inflammation, myofibroblasts activation, and extracellular matrix (ECM) deposition. Lipotoxicity oxidative stress are the driving force for loss of including tubules, glomerulus, endothelium. NLRP3 inflammasome signaling, MAPK PI3K/Akt RAAS signaling involves in lipotoxicity. The upregulated Nox expression decreased Nrf2 result directly. injured resident cells release proinflammatory cytokines chemokines to recruit immune such as macrophages from bone marrow. NF-κB JAK-STAT Toll-like receptor cGAS-STING major pathways mediate inflammation inflammatory cells. produce secret great number profibrotic TGF-β1, Wnt ligands, angiotensin II. TGF-β Notch evoke activation promote generation ECM. potential therapies targeted these also introduced here. In this review, we update key lipotoxicity, stress, kidneys with injury, drugs based on latest studies. Unifying will be instrumental advance further basic clinical investigation CKD.

Language: Английский

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Wnt/β‐catenin/RAS signaling mediates age‐related renal fibrosis and is associated with mitochondrial dysfunction

Aging Cell, Journal Year: 2019, Volume and Issue: 18(5)

Published: July 18, 2019

Abstract Renal fibrosis is the common pathological feature in a variety of chronic kidney diseases. Aging highly associated with progression renal fibrosis. Among several determinants, mitochondrial dysfunction plays an important role aging. However, underlying mechanisms age‐related are not elucidated. Herein, we found that Wnt/β‐catenin signaling and renin–angiotensin system (RAS) activity were upregulated aging kidneys. Concomitantly, mass functions impaired Ectopic expression Klotho, antagonist endogenous activity, abolished d ‐galactose ( ‐gal)‐induced accelerated mouse model significantly protected by preserving diminishing production reactive oxygen species. In established model, dickkopf 1, more specific Wnt inhibitor, mitochondria‐targeted antioxidant mitoquinone restored attenuated tubular senescence human proximal cell line (HKC‐8), ectopic Wnt1 decreased biogenesis induced mitochondria, triggered cellular senescence. Moreover, ‐gal transduction signaling, which further activated angiotensin type 1 receptor (AT1), then increased HKC‐8 cells primary cultured cells. These effects inhibited AT1 blocker losartan. results suggest inhibition RAS could slow onset Taken together, our indicate Wnt/β‐catenin/RAS mediates dysfunction.

Language: Английский

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Ovarian cancer stem cells and macrophages reciprocally interact through the WNT pathway to promote pro-tumoral and malignant phenotypes in 3D engineered microenvironments

Journal for ImmunoTherapy of Cancer, Journal Year: 2019, Volume and Issue: 7(1)

Published: July 19, 2019

Background

Innate immune cells such as macrophages are abundantly present within malignant ascites, where they share the microenvironment with ovarian cancer stem (CSC).

Methods

To mimic this ascites microenvironment, we created a hanging-drop hetero-spheroid model to bring CSCs and in close association. Within these hetero-spheroids, CD68⁺ (derived from U937 or peripheral blood monocytes) make up ~ 20% of population, while rest high grade serous cell line, OVCAR3).

Results

Our results indicate that drive upregulation M2 macrophage marker CD206 compared bulk cells, implying an inherently more immuno-suppressive program. Moreover, increased maintenance elevated aldehyde dehydrogenase (ALDH) activity is noted hetero-spheroids include pre-polarized CD206⁺ macrophages, reciprocal interaction drives pro-tumoral activation well CSC self-renewal. Consistent enriched CSCs, also observe levels IL-10 IL-6 cytokines CSC/M2-macrophage hetero-spheroids. less sensitive chemotherapeutic agent carboplatin subsequently invasive transwell assays. Using inhibitors WNT secretion both found CSC-derived ligands drove activation, that, conversely, macrophage-derived ALDH⁺ compartment Upon examination specific ligand expression monocyte-derived system, observed significant elevation gene for WNT5B. In co-cultured increases several were observed, increase was significantly inhibited when WNT5B knocked down macrophages.

Conclusions

data implies macrophage- initiated signaling could play role stemness, resulting phenotypes chemoresistance invasiveness. paracrine during CSC/M2 constitutes positive feedback loop likely contributes aggressive phenotype, which makes pathway potential target reduce compartments tumor microenvironment.

Language: Английский

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Cellular mechanotransduction in health and diseases: from molecular mechanism to therapeutic targets

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: July 31, 2023

Abstract Cellular mechanotransduction, a critical regulator of numerous biological processes, is the conversion from mechanical signals to biochemical regarding cell activities and metabolism. Typical cues in organisms include hydrostatic pressure, fluid shear stress, tensile force, extracellular matrix stiffness or tissue elasticity, viscosity. Mechanotransduction has been expected trigger multiple such as embryonic development, repair regeneration. However, prolonged excessive stimulation can result pathological multi-organ fibrosis, tumorigenesis, cancer immunotherapy resistance. Although associations between normal homeostasis diseases have identified, regulatory mechanisms among different are not yet comprehensively illustrated, no effective therapies currently available targeting cue-related signaling. This review systematically summarizes characteristics typical conditions with updated evidence. The key effectors responding stimulations listed, Piezo channels, integrins, Yes-associated protein (YAP) /transcriptional coactivator PDZ-binding motif (TAZ), transient receptor potential vanilloid 4 (TRPV4). We also reviewed signaling pathways, therapeutic targets cutting-edge clinical applications related cues.

Language: Английский

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Long noncoding RNA LINC00662 promotes M2 macrophage polarization and hepatocellular carcinoma progression via activating Wnt/β‐catenin signaling

Molecular Oncology, Journal Year: 2019, Volume and Issue: 14(2), P. 462 - 483

Published: Dec. 2, 2019

Tumor‐associated macrophages have important roles in hepatocellular carcinoma (HCC) initiation and progression. Long noncoding RNAs (lncRNAs) also been reported to be involved HCC. In this study, we explored how lncRNA LINC00662 may influence HCC progression through both tumor cell‐dependent macrophage‐dependent mechanisms. was found upregulated HCC, high levels correlated with poor survival of patients. WNT3A expression secretion via competitively binding miR‐15a, miR‐16, miR‐107. Through inducing secretion, activated Wnt/β‐catenin signaling cells an autocrine manner further promoted cell proliferation, cycle, invasion, while repressing apoptosis. addition, acting a paracrine M2 macrophage polarization. Via activating polarization, significantly growth metastasis vivo . Hence, targeting provide novel therapeutic strategy against

Language: Английский

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Ganoderic acid hinders renal fibrosis via suppressing the TGF-β/Smad and MAPK signaling pathways

Acta Pharmacologica Sinica, Journal Year: 2019, Volume and Issue: 41(5), P. 670 - 677

Published: Dec. 5, 2019

Language: Английский

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