Cathepsin C Is Involved in Macrophage M1 Polarization via p38/MAPK Pathway in Sudden Cardiac Death

Dai, Jialin; Liu, Jiangjin; Zhang, Qiong; An, Yang; Xia, Bing; Wan, Changwu; Zhang, Yuanyuan; Yu, Yu; Wang, Jie

doi:10.1155/2021/6139732

Cited by 14 publications

(15 citation statements)

References 24 publications

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“…2B ). As the MAPK pathway includes three main kinases, MAPK kinase kinase, MAPK kinase and MAPK, and the ERK-MAPK/P38-MAPK pathway were confirmed as important signaling cascades that plays crucial roles in angiogenesis/ macrophage polarization [ 29 , 30 ]. Then, we give a conjecture that the physiological purpose of generating SEVs accumulating miR-6750 can regulate both angiogenesis and macrophage polarization to inhibit NPC metastasis.…”

Section: Resultsmentioning

confidence: 99%

SEVs-mediated miR-6750 transfer inhibits pre-metastatic niche formation in nasopharyngeal carcinoma by targeting M6PR

et al. 2023

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Reliable detection of circulating small extracellular vesicles (SEVs) and their miRNA cargo has been needed to develop potential specific non-invasive diagnostic and therapeutic marker for cancer metastasis. Here, we detected miR-6750, the precise molecular function of which was largely unknown, was significantly enriched in serum-SEVs from normal volunteers vs. patients with nasopharyngeal carcinoma (NPC). And we determined that miR-6750-SEVs attenuated NPC metastasis. Subsequently, miR-6750-SEVs was proven to inhibit angiogenesis and activate macrophage toward to M1 phenotype to inhibit pre-metastatic niche formation. After analyzing the expression level of miR-6750 in NPC cells, HUVECs and macrophage, we found that once miR-6750 level in NPC cells was close to or higher than normal nasopharyngeal epithelial cells (NP69), miR-6750-SEVs would be transferred from NPC cells to macrophage and then to HUVECs to modulate metastatic niche. Moreover, in vitro assays and BALB/c mouse tumor models revealed that miR-6750 directly targeted mannose 6-phosphate receptor (M6PR). Taken together, our findings revealed that miR-6750-M6PR axis can mediate NPC metastasis by remodeling tumor microenvironment (TME) via SEVs, which give novel sights to pathogenesis of NPC.

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Section: Resultsmentioning

confidence: 99%

SEVs-mediated miR-6750 transfer inhibits pre-metastatic niche formation in nasopharyngeal carcinoma by targeting M6PR

et al. 2023

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“…The mechanism by which the SA/BG hydrogel promoted M2 polarization remains unclear. As for the MAPK signaling pathway, it has been previously reported that the p38/MAPK pathway plays a role in IL-4-induced M2 polarization; however, some research studies also have demonstrated that p38/MAPK is involved in M1 polarization . Therefore, the role of the MAPK signaling pathway in SA/SrBG hydrogel-induced regulation of macrophage phenotype deserves to be studied in further experiments.…”

Section: Discussionmentioning

confidence: 98%

“…As for the MAPK signaling pathway, it has been previously reported that the p38/MAPK pathway plays a role in IL-4-induced M2 polarization; however, some research studies also have demonstrated that p38/MAPK is involved in M1 polarization. 53 Therefore, the role of the MAPK signaling pathway in SA/SrBG hydrogelinduced regulation of macrophage phenotype deserves to be studied in further experiments. It was also reported that the SA/BG composite hydrogel could enhance the secretion of TGFβ from the M2 macrophages, which is known to play an important role in chondrogenesis.…”

Section: Discussionmentioning

confidence: 99%

Anti-Inflammatory and Prochondrogenic In Situ-Formed Injectable Hydrogel Crosslinked by Strontium-Doped Bioglass for Cartilage Regeneration

Cai

Song

et al. 2021

ACS Appl. Mater. Interfaces

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Directed differentiation of bone marrow mesenchymal stem cells (BMSCs) toward chondrogenesis plays a predominant role in cartilage repair. However, the uncontrolled inflammatory response to implants is found to impair the stability of scaffolds and the cartilage regeneration outcome. Herein, we fabricated an injectable hydrogel crosslinked by strontium-doped bioglass (SrBG) to modulate both human BMSC (hBMSC) differentiation and the inflammatory response. The results revealed that the introduction of Sr ions could simultaneously enhance the proliferation of hBMSCs, upregulate cartilage-specific gene expression, and improve the secretion of glycosaminoglycan. Moreover, after cultured with SA/ SrBG extracts in vitro, a majority of macrophages were polarized toward the M2 phenotype and subsequently facilitated the chondrogenic differentiation of hBMSCs. Furthermore, after the composite hydrogel was injected into a cartilage defect model, neonatal cartilage-like tissues with a smooth surface and tight integration with original tissues could be found. This study suggests that the synergistic strategy based on an enhanced differentiation ability and a regulated inflammatory response is promising and may lead the way to new anti-inflammatory biomaterials.

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“…Therefore, data from both animal (Hu et al 2019 ) and human (Dai et al 2021 ) studies have revealed that pathological processes resulting in heart diseases are associated with M1 macrophage polarisation, concomitantly with inhibition of M2 macrophage recruitment in the heart. For instance, Liu et al ( 2015a , b ) demonstrated M1 polarisation in a rat model of myocardial infarction along with disordered Ca 2+ waves, which stimulated the extracellular Ca 2+ receptor, CaSR, which in turn activated the NLRP3 (nucleotide-binding oligomerisation domain, leucine-rich repeats, pyrin domain-containing protein 3) inflammasome via phospholipase C (PLC)—inositol 1,4,5-triphosphate (IP3) pathway (Liu et al 2015a ).…”

Section: Contemporary View Of the Mechanisms Of Cardiac Inflammation ...mentioning

confidence: 99%

Cellular mechanisms and molecular pathways linking bitter taste receptor signalling to cardiac inflammation, oxidative stress, arrhythmia and contractile dysfunction in heart diseases

2022

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Heart diseases and related complications constitute a leading cause of death and socioeconomic threat worldwide. Despite intense efforts and research on the pathogenetic mechanisms of these diseases, the underlying cellular and molecular mechanisms are yet to be completely understood. Several lines of evidence indicate a critical role of inflammatory and oxidative stress responses in the development and progression of heart diseases. Nevertheless, the molecular machinery that drives cardiac inflammation and oxidative stress is not completely known. Recent data suggest an important role of cardiac bitter taste receptors (TAS2Rs) in the pathogenetic mechanism of heart diseases. Independent groups of researchers have demonstrated a central role of TAS2Rs in mediating inflammatory, oxidative stress responses, autophagy, impulse generation/propagation and contractile activities in the heart, suggesting that dysfunctional TAS2R signalling may predispose to cardiac inflammatory and oxidative stress disorders, characterised by contractile dysfunction and arrhythmia. Moreover, cardiac TAS2Rs act as gateway surveillance units that monitor and detect toxigenic or pathogenic molecules, including microbial components, and initiate responses that ultimately culminate in protection of the host against the aggression. Unfortunately, however, the molecular mechanisms that link TAS2R sensing of the cardiac milieu to inflammatory and oxidative stress responses are not clearly known. Therefore, we sought to review the possible role of TAS2R signalling in the pathophysiology of cardiac inflammation, oxidative stress, arrhythmia and contractile dysfunction in heart diseases. Potential therapeutic significance of targeting TAS2R or its downstream signalling molecules in cardiac inflammation, oxidative stress, arrhythmia and contractile dysfunction is also discussed.

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Cathepsin C Is Involved in Macrophage M1 Polarization via p38/MAPK Pathway in Sudden Cardiac Death

Cited by 14 publications

References 24 publications

SEVs-mediated miR-6750 transfer inhibits pre-metastatic niche formation in nasopharyngeal carcinoma by targeting M6PR

SEVs-mediated miR-6750 transfer inhibits pre-metastatic niche formation in nasopharyngeal carcinoma by targeting M6PR

Anti-Inflammatory and Prochondrogenic In Situ-Formed Injectable Hydrogel Crosslinked by Strontium-Doped Bioglass for Cartilage Regeneration

Cellular mechanisms and molecular pathways linking bitter taste receptor signalling to cardiac inflammation, oxidative stress, arrhythmia and contractile dysfunction in heart diseases

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