-
Science Signaling Jul 2023Uncontrolled inflammation is linked to poor outcomes in sepsis and wound healing, both of which proceed through distinct inflammatory and resolution phases. Eicosanoids...
Uncontrolled inflammation is linked to poor outcomes in sepsis and wound healing, both of which proceed through distinct inflammatory and resolution phases. Eicosanoids are a class of bioactive lipids that recruit neutrophils and other innate immune cells. The interaction of ceramide 1-phosphate (C1P) with the eicosanoid biosynthetic enzyme cytosolic phospholipase A (cPLA) reduces the production of a subtype of eicosanoids called oxoeicosanoids. We investigated the effect of shifting the balance in eicosanoid biosynthesis on neutrophil polarization and function. Knockin mice expressing a cPLA mutant lacking the C1P binding site (α mice) showed enhanced and sustained neutrophil infiltration into wounds and the peritoneum during the inflammatory phase of wound healing and sepsis, respectively. The mice exhibited improved wound healing and reduced susceptibility to sepsis, which was associated with an increase in anti-inflammatory N2-type neutrophils demonstrating proresolution behaviors and a decrease in proinflammatory N1-type neutrophils. The N2 polarization of α neutrophils resulted from increased oxoeicosanoid biosynthesis and autocrine signaling through the oxoeicosanoid receptor OXER1 and partially depended on OXER1-dependent inhibition of the pentose phosphate pathway (PPP). Thus, C1P binding to cPLAα suppresses neutrophil N2 polarization, thereby impairing wound healing and the response to sepsis.
Topics: Animals; Mice; Neutrophils; Sepsis; Autocrine Communication; Group IV Phospholipases A2; Inflammation
PubMed: 37433004
DOI: 10.1126/scisignal.add6527 -
Reproduction in Domestic Animals =... Jul 2020Dog reproductive cycle is unique among other mammals in that females experience long and variable periods of ovarian inactivity. Neuroendocrine controls of the... (Review)
Review
Dog reproductive cycle is unique among other mammals in that females experience long and variable periods of ovarian inactivity. Neuroendocrine controls of the reproductive cycle have been thoroughly studied in the dog. However, there is little information regarding endocrine, paracrine and autocrine controls of dog ovarian folliculogenesis. Advancements in the understanding of mechanisms regulating dog ovarian follicle development will be helpful in the establishment of an approach to control cyclicity in this species. Furthermore, such information will likely be useful for the establishment of an in vitro follicle culture system to preserve fertility of genetically valuable disease models or endangered canids. This review highlights current knowledge on dog folliculogenesis with emphasis on endocrine, paracrine and autocrine controls of follicular development.
Topics: Animals; Autocrine Communication; Dogs; Endocrine Glands; Female; Ovarian Follicle; Paracrine Communication; Reproduction
PubMed: 32347633
DOI: 10.1111/rda.13657 -
Nature Communications Oct 2020Development of high throughput single-cell sequencing technologies has made it cost-effective to profile thousands of cells from diverse samples containing multiple cell...
Development of high throughput single-cell sequencing technologies has made it cost-effective to profile thousands of cells from diverse samples containing multiple cell types. To study how these different cell types work together, here we develop NATMI (Network Analysis Toolkit for Multicellular Interactions). NATMI uses connectomeDB2020 (a database of 2293 manually curated ligand-receptor pairs with literature support) to predict and visualise cell-to-cell communication networks from single-cell (or bulk) expression data. Using multiple published single-cell datasets we demonstrate how NATMI can be used to identify (i) the cell-type pairs that are communicating the most (or most specifically) within a network, (ii) the most active (or specific) ligand-receptor pairs active within a network, (iii) putative highly-communicating cellular communities and (iv) differences in intercellular communication when profiling given cell types under different conditions. Furthermore, analysis of the Tabula Muris (organism-wide) atlas confirms our previous prediction that autocrine signalling is a major feature of cell-to-cell communication networks, while also revealing that hundreds of ligands and their cognate receptors are co-expressed in individual cells suggesting a substantial potential for self-signalling.
Topics: Age Factors; Animals; Autocrine Communication; Cell Communication; Computational Biology; Data Visualization; Databases, Factual; Female; Ligands; Mammary Glands, Animal; Mice; Proteins; Single-Cell Analysis; Software; User-Computer Interface
PubMed: 33024107
DOI: 10.1038/s41467-020-18873-z -
Circulation Research Jun 2015Cardiac hypertrophy is characterized by complex multicellular alterations, such as cardiomyocyte growth, angiogenesis, fibrosis, and inflammation. The heart consists of... (Review)
Review
Cardiac hypertrophy is characterized by complex multicellular alterations, such as cardiomyocyte growth, angiogenesis, fibrosis, and inflammation. The heart consists of myocytes and nonmyocytes, such as fibroblasts, vascular cells, and blood cells, and these cells communicate with each other directly or indirectly via a variety of autocrine or paracrine mediators. Accumulating evidence has suggested that nonmyocytes actively participate in the development of cardiac hypertrophy. In this review, recent progress in our understanding of the importance of nonmyocytes as a hub for induction of cardiac hypertrophy is summarized with an emphasis of the contribution of noncontact communication mediated by diffusible factors between cardiomyocytes and nonmyocytes in the heart.
Topics: Animals; Autocrine Communication; Blood Cells; Cardiomegaly; Cell Lineage; Endothelial Cells; Endothelin-1; Fibroblasts; Humans; Intercellular Signaling Peptides and Proteins; Macrophages; Mast Cells; Mice; MicroRNAs; Myocardium; Myocytes, Cardiac; Natriuretic Peptides; Paracrine Communication
PubMed: 26089366
DOI: 10.1161/CIRCRESAHA.117.305349 -
Molecular Immunology Apr 2017Most of the complement proteins in circulation are, by and large, synthesized in the liver. However data accumulated over the past several decades provide... (Review)
Review
Most of the complement proteins in circulation are, by and large, synthesized in the liver. However data accumulated over the past several decades provide incontrovertible evidence that some if not most of the individual complement proteins are also synthesized extrahepatically by activated as well as non-activated cells. The question that is finally being addressed by various investigators is: are the locally synthesized proteins solely responsible for the myriad of biological functions in situ without the contribution of systemic complement? The answer is probably "yes". Among the proteins that are synthesized locally, C1q takes center stage for several reasons. First, it is synthesized predominantly by potent antigen presenting cells such as monocytes, macrophages and dendritic cells (DCs), which by itself is a clue that it plays an important role in antigen presentation and/or DC maturation. Second, it is transiently anchored on the cell surface via a transmembrane domain located in its A chain before it is cleaved off and released into the pericellular milieu. The membrane-associated C1q in turn, is able to sense danger patterns via its versatile antigen-capturing globular head domains. More importantly, locally synthesized C1q has been shown to induce a plethora of biological functions through the induction of immunomodulatory molecules by an autocrine- or paracrine- mediated signaling in a manner that mimics those of TNFα. These include recognition of pathogen- and danger- associated molecular patterns, phagocytosis, angiogenesis, apoptosis and induction of cytokines or chemokines that are important in modulating the inflammatory response. The functional convergence between C1q and TNFα in turn is attributed to their shared genetic ancestry. In this paper, we will infer to the aforementioned "local-synthesis-for-local function" paradigm using as an example, the role played by locally synthesized C1q in autoimmunity in general and in systemic lupus erythematosus in particular.
Topics: Animals; Autocrine Communication; Complement C1q; Dendritic Cells; Humans; Immune Tolerance; Paracrine Communication
PubMed: 27914690
DOI: 10.1016/j.molimm.2016.11.003 -
BioMed Research International 2021When vascular endothelial cells are subjected to external stimuli, paracrine hormones and cytokines act on adjacent cells. The regulation of the biological behaviour of...
BACKGROUND
When vascular endothelial cells are subjected to external stimuli, paracrine hormones and cytokines act on adjacent cells. The regulation of the biological behaviour of cells is closely related to the maintenance of organ function and the occurrence and development of disease. However, it is unclear whether vascular endothelial cells affect the biological behaviour of cells involved in wound repair through autocrine and paracrine mechanisms and ultimately play a role in wound healing. We aimed to verify the effect of the autocrine and paracrine functions of vascular endothelial cells on wound healing.
MATERIALS AND METHODS
ELISA was used to detect platelet-derived growth factor, basic fibroblast growth factor, epidermal growth factor, and vascular endothelial growth factor in human umbilical vascular endothelial cell-conditioned medium (HUVEC-CM). Different concentrations of HUVEC-CM were used to treat different stem cells. CCK-8 and scratch assays were used to detect the proliferation and migration ability of each cell. A full-thickness dorsal skin defect model was established in mice, and skin wound healing was observed after the local injection of HUVEC-CM, endothelial cell medium (ECM), or normal saline. H&E staining and immunofluorescence were used to observe the gross morphology of the wound tissue, the epithelial cell migration distance, and the expression of CD3 and CD31.
RESULTS
HUVEC-CM promotes the proliferation and migration of epidermal stem cells, skin fibroblasts, bone marrow mesenchymal stem cells, and HUVECs themselves. Furthermore, HUVEC-CM can promote angiogenesis in mouse skin wounds and granulation tissue formation and can accelerate wound surface epithelialization and collagen synthesis, thereby promoting wound healing.
CONCLUSION
Our results clearly suggest that it is practicable and effective to promote wound healing with cytokines secreted by vascular endothelial cells in a mouse model.
Topics: Antigens, CD; Autocrine Communication; Biomarkers; Cell Movement; Cell Proliferation; Culture Media, Conditioned; Cytokines; Fibroblasts; Human Embryonic Stem Cells; Human Umbilical Vein Endothelial Cells; Humans; Mesenchymal Stem Cells; Paracrine Communication; Skin; Wound Healing
PubMed: 33937411
DOI: 10.1155/2021/6695663 -
Cells Aug 2021Annexin A1 is a 37 kDa phospholipid-binding protein that is expressed in many tissues and cell types, including leukocytes, lymphocytes and epithelial cells. Although... (Review)
Review
Annexin A1 is a 37 kDa phospholipid-binding protein that is expressed in many tissues and cell types, including leukocytes, lymphocytes and epithelial cells. Although Annexin A1 has been extensively studied for its anti-inflammatory activity, it has been shown that, in the cancer context, its activity switches from anti-inflammatory to pro-inflammatory. Remarkably, Annexin A1 shows pro-invasive and pro-tumoral properties in several cancers either by eliciting autocrine signaling in cancer cells or by inducing a favorable tumor microenvironment. Indeed, the signaling of the -terminal peptide of AnxA1 has been described to promote the switching of macrophages to the pro-tumoral M2 phenotype. Moreover, AnxA1 has been described to prevent the induction of antigen-specific cytotoxic T cell response and to play an essential role in the induction of regulatory T lymphocytes. In this way, Annexin A1 inhibits the anti-tumor immunity and supports the formation of an immunosuppressed tumor microenvironment that promotes tumor growth and metastasis. For these reasons, in this review we aim to describe the role of Annexin A1 in the establishment of the tumor microenvironment, focusing on the immunosuppressive and immunomodulatory activities of Annexin A1 and on its interaction with the epidermal growth factor receptor.
Topics: Animals; Annexin A1; Autocrine Communication; Humans; Immunity; Neoplasms; Tumor Microenvironment
PubMed: 34571894
DOI: 10.3390/cells10092245 -
International Journal of Molecular... Jan 2021Autocrine signaling is defined as the production and secretion of an extracellular mediator by a cell followed by the binding of that mediator to receptors on the same... (Review)
Review
Autocrine signaling is defined as the production and secretion of an extracellular mediator by a cell followed by the binding of that mediator to receptors on the same cell to initiate signaling. Autocrine stimulation often operates in autocrine loops, a type of interaction, in which a cell produces a mediator, for which it has receptors, that upon activation promotes expression of the same mediator, allowing the cell to repeatedly autostimulate itself (positive feedback) or balance its expression via regulation of a second factor that provides negative feedback. Autocrine signaling loops with positive or negative feedback are an important feature in cancer, where they enable context-dependent cell signaling in the regulation of growth, survival, and cell motility. A growth factor that is intimately involved in tumor development and progression and often produced by the cancer cells in an autocrine manner is transforming growth factor-β (TGF-β). This review surveys the many observations of autocrine TGF-β signaling in tumor biology, including data from cell culture and animal models as well as from patients. We also provide the reader with a critical discussion on the various experimental approaches employed to identify and prove the involvement of autocrine TGF-β in a given cellular response.
Topics: Animals; Autocrine Communication; Biomedical Research; Feedback, Physiological; Gene Expression Regulation, Neoplastic; Humans; Neoplasms; Receptors, Transforming Growth Factor beta; Research Design; Transforming Growth Factor beta
PubMed: 33478130
DOI: 10.3390/ijms22020977 -
Cells Aug 2021For multi-cellular organisms to organize tissues, their cells must communicate with each other [...].
For multi-cellular organisms to organize tissues, their cells must communicate with each other [...].
Topics: Animals; Autocrine Communication; Fibroblast Growth Factors; Humans; Neoplasms; Paracrine Communication; Receptors, Fibroblast Growth Factor; Signal Transduction
PubMed: 34571880
DOI: 10.3390/cells10092231 -
Current Opinion in Neurobiology Aug 2018Although retrograde neurotrophin signaling has provided an immensely influential paradigm for understanding growth factor signaling in the nervous system, recent studies... (Review)
Review
Although retrograde neurotrophin signaling has provided an immensely influential paradigm for understanding growth factor signaling in the nervous system, recent studies indicate that growth factors also signal via cell-autonomous, or autocrine, mechanisms. Autocrine signals have been discovered in many neuronal contexts, providing insights into their regulation and function. The growing realization of the importance of cell-autonomous signaling stems from advances in both conditional genetic approaches and in sophisticated analyses of growth factor dynamics, which combine to enable rigorous in vivo dissection of signaling pathways. Here we review recent studies defining autocrine roles for growth factors such as BDNF, and classical morphogens, including Wnts and BMPs, in regulating neuronal development and plasticity. Collectively, these studies highlight an intimate relationship between activity-dependent autocrine signaling and synaptic plasticity, and further suggest a common principle for coordinating paracrine and autocrine signaling in the nervous system.
Topics: Animals; Autocrine Communication; Neurons; Signal Transduction
PubMed: 29547843
DOI: 10.1016/j.conb.2018.03.002