Role of connexin 43 in different forms of intercellular communication – gap junctions, extracellular vesicles and tunnelling nanotubes

Journal of Cell Science, Journal Year: 2017, Volume and Issue: 130(21), P. 3619 - 3630

Published: Oct. 13, 2017

ABSTRACT Communication is important to ensure the correct and efficient flow of information, which required sustain active social networks. A fine-tuned communication between cells vital maintain homeostasis function multicellular or unicellular organisms in a community environment. Although there are different levels complexity, intercellular communication, prokaryotes mammalians, can occur through secreted molecules (either soluble encapsulated vesicles), tubular structures connecting close channels that link cytoplasm adjacent cells. In mammals, these types serve purposes, may involve distinct factors mediated by extracellular vesicles, tunnelling nanotubes gap junctions. Recent studies have shown connexin 43 (Cx43, also known as GJA1), transmembrane protein initially described junction protein, participates all forms communication; this emphasizes concept adopting strategies maximize potential available resources reutilizing same factor scenarios. Review, we provide an overview most recent advances regarding role Cx43

Language: Английский

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Potential Use of Exosomes as Diagnostic Biomarkers and in Targeted Drug Delivery: Progress in Clinical and Preclinical Applications

ACS Biomaterials Science & Engineering, Journal Year: 2021, Volume and Issue: 7(6), P. 2106 - 2149

Published: May 14, 2021

Exosomes are cell-derived vesicles containing heterogeneous active biomolecules such as proteins, lipids, mRNAs, receptors, immune regulatory molecules, and nucleic acids. They typically range in size from 30 to 150 nm diameter. An exosome's surfaces can be bioengineered with antibodies, fluorescent dye, peptides, tailored for small molecule large biologics. have enormous potential a drug delivery vehicle due enhanced biocompatibility, excellent payload capability, reduced immunogenicity compared alternative polymeric-based carriers. Because of targeting specificity, exosomes capable delivering their cargo exosome-recipient cells. Additionally, potentially act early stage disease diagnostic tools the exosome carries various protein biomarkers associated specific disease. In this review, we summarize recent progress on composition, biological characterization, isolation techniques. Finally, outline clinical applications preclinical advancement provide an outlook importance use targeted delivery, biomarker study, vaccine development.

Language: Английский

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Connexins in cancer: bridging the gap to the clinic

Oncogene, Journal Year: 2019, Volume and Issue: 38(23), P. 4429 - 4451

Published: Feb. 27, 2019

Gap junctions comprise arrays of intercellular channels formed by connexin proteins and provide for the direct communication between adjacent cells. This type permits coordination cellular activities plays key roles in control cell growth differentiation maintenance tissue homoeostasis. After more than 50 years, deciphering links among connexins, gap cancer, researchers are now beginning to translate this knowledge clinic. The emergence new strategies targeting, combined with an improved understanding molecular bases underlying dysregulation connexins during cancer development, offers novel opportunities clinical applications. However, different isoforms have diverse channel-dependent -independent functions that stage specific. can elicit both pro- anti-tumorigenic effects engender significant challenges path towards personalised medicine. Here, we review current role particular focus on recent progress made determining their prognostic therapeutic potential.

Language: Английский

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Myeloid‐Cell–Specific IL‐6 Signaling Promotes MicroRNA‐223‐Enriched Exosome Production to Attenuate NAFLD‐Associated Fibrosis

Hepatology, Journal Year: 2020, Volume and Issue: 74(1), P. 116 - 132

Published: Nov. 25, 2020

Background ands Aims NAFLD is associated with elevation of many cytokines, particularly IL‐6; however, the role IL‐6 in remains obscure. The aim this study was to examine how myeloid‐specific signaling affects by regulation antifibrotic microRNA‐223 (miR‐223) myeloid cells. Approach and Results Patients or NASH healthy controls were recruited, serum soluble receptor α (sIL‐6Rα) measured. Compared controls, sIL‐6Rα levels elevated NAFLD/NASH patients. correlated positively number circulating leukocytes monocytes. investigated Il6 knockout (KO) A ( Il6ra ) conditional KO mice after high‐fat diet (HFD) feeding. HFD‐fed had worse liver injury fibrosis, but less inflammation, compared wild‐type mice. Hepatocyte‐specific more steatosis injury, whereas a lower hepatic infiltrating macrophages (IMs) neutrophils increased cell death these cells, greater fibrosis (LF), than WT Mechanistically, LF HFD‐fed, attributable reduction miR‐223 subsequent up‐regulation target gene, transcriptional activator PDZ‐binding motif (TAZ), well‐known factor promote fibrosis. In vitro , treatment up‐regulated exosome biogenesis‐related genes subsequently promoted release miR‐223‐enriched exosomes that able reduce profibrotic TAZ expression hepatocytes exosomal transfer. Finally, each other Conclusions Myeloid‐specific inhibits through transfer into hepatocytes, providing therapeutic targets for therapy.

Language: Английский

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The role of Exosomal miRNAs in cancer

Journal of Translational Medicine, Journal Year: 2022, Volume and Issue: 20(1)

Published: Jan. 3, 2022

Exosomal miRNAs have attracted much attention due to their critical role in regulating genes and the altered expression of virtually all cancers affecting humans (Sun et al. Mol Cancer 17(1):14, 2018). modulate processes that interfere with cancer immunity microenvironment, are significantly involved tumor growth, invasion, metastasis, angiogenesis drug resistance. Fully investigating detailed mechanism occurrence development various could help not only treatment but also prevention malignant diseases. The current review highlighted recently published advances regarding cancer-derived exosomes, e.g., sorting delivery mechanisms for RNAs. cell-to-cell communication, impacting angiogenesis, metastasis multiple biological features, were discussed. Finally, potential exosomal as diagnostic prognostic molecular markers was summarized, well usefulness detecting resistance therapeutic agents.

Language: Английский

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