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Article ; Online: Anti-oncostatin M antibody inhibits the pro-malignant effects of oncostatin M receptor overexpression in squamous cell carcinoma.

Kucia-Tran, Justyna A / Tulkki, Valtteri / Scarpini, Cinzia G / Smith, Stephen / Wallberg, Maja / Paez-Ribes, Marta / Araujo, Angela M / Botthoff, Jan / Feeney, Maria / Hughes, Katherine / Caffarel, Maria M / Coleman, Nicholas

The Journal of pathology

2018 Volume 244, Issue 3, Page(s) 283–295

Abstract: The oncostatin M (OSM) receptor (OSMR) shows frequent gene copy number gains and overexpression ...

Abstract	The oncostatin M (OSM) receptor (OSMR) shows frequent gene copy number gains and overexpression in cervical squamous cell carcinomas (SCCs), associated with adverse clinical outcomes. In SCC cells that overexpress OSMR, the major ligand OSM induces multiple pro-malignant effects, including invasion, secretion of angiogenic factors, and metastasis. Here, we demonstrate, for the first time, that OSMR overexpression in SCC cells activates cell-autonomous feed-forward signalling, via further expression of OSMR and OSM and sustained STAT3 activation, despite expression of the negative regulator suppressor of cytokine signalling 3 (SOCS3). The pro-malignant effects associated with OSMR overexpression are critically mediated by JAK-STAT3 activation, which is induced by exogenous OSM and also by autocrine OSM-OSMR interactions. Importantly, specific inhibition of OSM-OSMR interactions by neutralizing antibodies significantly inhibits STAT3 activation and feed-forward signalling, leading to reduced invasion, angiogenesis, and metastasis. Our findings are supported by data from 1254 clinical SCC samples, in which OSMR levels correlated with multiple cognate genes, including OSM, STAT3, and downstream targets. These data strongly support the development of OSM-OSMR-blocking antibodies as biologically targeted therapies against SCCs of the cervix and other anatomical sites. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
MeSH term(s)	Animals ; Antineoplastic Agents, Immunological/pharmacology ; Autocrine Communication ; Cell Line, Tumor ; Female ; Gene Expression Regulation, Neoplastic ; Head and Neck Neoplasms/drug therapy ; Head and Neck Neoplasms/immunology ; Head and Neck Neoplasms/metabolism ; Head and Neck Neoplasms/pathology ; Humans ; Janus Kinase 2/genetics ; Janus Kinase 2/metabolism ; Lung Neoplasms/drug therapy ; Lung Neoplasms/immunology ; Lung Neoplasms/metabolism ; Lung Neoplasms/pathology ; Mice, Inbred NOD ; Mice, SCID ; Oncostatin M/genetics ; Oncostatin M/metabolism ; Oncostatin M Receptor beta Subunit/antagonists & inhibitors ; Oncostatin M Receptor beta Subunit/genetics ; Oncostatin M Receptor beta Subunit/immunology ; Oncostatin M Receptor beta Subunit/metabolism ; Phosphorylation ; STAT3 Transcription Factor/genetics ; STAT3 Transcription Factor/metabolism ; Signal Transduction ; Squamous Cell Carcinoma of Head and Neck/drug therapy ; Squamous Cell Carcinoma of Head and Neck/immunology ; Squamous Cell Carcinoma of Head and Neck/metabolism ; Squamous Cell Carcinoma of Head and Neck/pathology ; Suppressor of Cytokine Signaling 3 Protein/genetics ; Suppressor of Cytokine Signaling 3 Protein/metabolism ; Up-Regulation ; Uterine Cervical Neoplasms/drug therapy ; Uterine Cervical Neoplasms/immunology ; Uterine Cervical Neoplasms/metabolism ; Uterine Cervical Neoplasms/pathology ; Xenograft Model Antitumor Assays
Chemical Substances	Antineoplastic Agents, Immunological ; OSM protein, human ; OSMR protein, human ; Oncostatin M Receptor beta Subunit ; SOCS3 protein, human ; STAT3 Transcription Factor ; STAT3 protein, human ; Suppressor of Cytokine Signaling 3 Protein ; Oncostatin M (106956-32-5) ; JAK2 protein, human (EC 2.7.10.2) ; Janus Kinase 2 (EC 2.7.10.2)
Language	English
Publishing date	2018-01-09
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	3119-7
ISSN	1096-9896 ; 0022-3417
ISSN (online)	1096-9896
ISSN	0022-3417
DOI	10.1002/path.5010
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Article ; Online: Overexpression of the oncostatin-M receptor in cervical squamous cell carcinoma is associated with epithelial-mesenchymal transition and poor overall survival.

Kucia-Tran, Justyna A / Tulkki, Valtteri / Smith, Stephen / Scarpini, Cinzia G / Hughes, Katherine / Araujo, Angela M / Yan, Ka Yin Matthew / Botthof, Jan / Pérez-Gómez, Eduardo / Quintanilla, Miguel / Cuschieri, Kate / Caffarel, Maria M / Coleman, Nicholas

British journal of cancer

2016 Volume 115, Issue 2, Page(s) 212–222

Abstract: Background: Copy-number gain of the oncostatin-M receptor (OSMR) occurs frequently in cervical ... overexpression renders cervical SCC cells more sensitive to the major ligand oncostatin-M (OSM), which increases ...

Abstract	Background: Copy-number gain of the oncostatin-M receptor (OSMR) occurs frequently in cervical squamous cell carcinoma (SCC) and is associated with adverse clinical outcome. We previously showed that OSMR overexpression renders cervical SCC cells more sensitive to the major ligand oncostatin-M (OSM), which increases migration and invasion in vitro. We hypothesised that a major contribution to this phenotype would come from epithelial-mesenchymal transition (EMT). Methods: We performed a comprehensive integrated study, involving in vitro cell line studies, in vivo animal models and numerous clinical samples from a variety of anatomical sites. Results: In independent sets of cervical, head/neck and lung SCC tissues, OSMR expression levels correlated with multiple EMT-associated phenotypic markers and transcription factors. OSM treatment of OSMR overexpressing cervical SCC cells produced consistent EMT changes and increased tumour sphere formation in suspension culture. In a mouse model, OSMR overexpressing SCC cells treated with OSM showed significant increases in lung colonisation. The biological effects of exogenous OSM were mirrored by highly significant adverse overall survival in cervical SCCs with OSMR overexpression (N=251). Conclusions: OSM:OSMR interactions are able to induce EMT, increased cancer stem cell-like properties and enhanced lung colonisation in SCC cells. These changes are likely to contribute to the highly significant adverse outcome associated with OSMR overexpression in cervical SCCs.
MeSH term(s)	Animals ; Carcinoma, Squamous Cell/metabolism ; Carcinoma, Squamous Cell/pathology ; Cell Line, Tumor ; Epithelial-Mesenchymal Transition ; Female ; Heterografts ; Humans ; Janus Kinase 2/metabolism ; Mice ; Neoplasm Metastasis ; Receptors, Oncostatin M/metabolism ; STAT3 Transcription Factor/metabolism ; Survival Analysis ; Uterine Cervical Neoplasms/metabolism ; Uterine Cervical Neoplasms/pathology
Chemical Substances	Receptors, Oncostatin M ; STAT3 Transcription Factor ; STAT3 protein, human ; JAK2 protein, human (EC 2.7.10.2) ; Janus Kinase 2 (EC 2.7.10.2)
Language	English
Publishing date	2016-06-28
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80075-2
ISSN	1532-1827 ; 0007-0920
ISSN (online)	1532-1827
ISSN	0007-0920
DOI	10.1038/bjc.2016.199
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Article ; Online: Academic Intelligence: Learning Analytics in a Learning Organization.

Kucia, Margaret M

The journal of physician assistant education : the official journal of the Physician Assistant Education Association

2021 Volume 32, Issue 2, Page(s) 131–134

MeSH term(s)	Humans ; Intelligence ; Learning ; Physician Assistants/education
Language	English
Publishing date	2021-05-02
Publishing country	United States
Document type	Journal Article
ZDB-ID	2620682-1
ISSN	1941-9449 ; 1941-9430
ISSN (online)	1941-9449
ISSN	1941-9430
DOI	10.1097/JPA.0000000000000361
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Article ; Online: Extracellular Adenosine Triphosphate (eATP) and Its Metabolite, Extracellular Adenosine (eAdo), as Opposing "Yin-Yang" Regulators of Nlrp3 Inflammasome in the Trafficking of Hematopoietic Stem/Progenitor Cells.

Ratajczak, Mariusz Z / Kucia, Magda

Frontiers in immunology

2021 Volume 11, Page(s) 603942

Abstract: Nlrp3 inflammasome plays a pleiotropic role in hematopoietic cells. On the one hand, physiological activation of this intracellular protein complex is crucial to maintaining normal hematopoiesis and the trafficking of hematopoietic stem progenitor cells ( ...

Abstract	Nlrp3 inflammasome plays a pleiotropic role in hematopoietic cells. On the one hand, physiological activation of this intracellular protein complex is crucial to maintaining normal hematopoiesis and the trafficking of hematopoietic stem progenitor cells (HSPCs). On the other hand, its hyperactivation may lead to cell death by pyroptosis, and prolonged activity is associated with sterile inflammation of the BM and, as a consequence, with the HSPCs aging and origination of myelodysplasia and leukemia. Thus, we need to understand better this protein complex's actions to define the boundaries of its safety window and study the transition from being beneficial to being detrimental. As demonstrated, the Nlrp3 inflammasome is expressed and active both in HSPCs and in the non-hematopoietic cells that are constituents of the bone marrow (BM) microenvironment. Importantly, the Nlrp3 inflammasome responds to mediators of purinergic signaling, and while extracellular adenosine triphosphate (eATP) activates this protein complex, its metabolite extracellular adenosine (eAdo) has the opposite effect. In this review, we will discuss and focus on the physiological consequences of the balance between eATP and eAdo in regulating the trafficking of HSPCs in an Nlrp3 inflammasome-dependent manner, as seen during pharmacological mobilization from BM into peripheral blood (PB) and in the reverse mechanism of homing from PB to BM and engraftment. We propose that both mediators of purinergic signaling and the Nlrp3 inflammasome itself may become important therapeutic targets in optimizing the trafficking of HSPCs in clinical settings.
MeSH term(s)	Adenosine/metabolism ; Adenosine Triphosphate/metabolism ; Animals ; Cell Survival ; Hematopoietic Stem Cell Mobilization/adverse effects ; Hematopoietic Stem Cell Transplantation/adverse effects ; Hematopoietic Stem Cells/drug effects ; Hematopoietic Stem Cells/immunology ; Hematopoietic Stem Cells/metabolism ; Humans ; Inflammasomes/metabolism ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism ; Signal Transduction ; Stem Cell Niche ; Treatment Outcome
Chemical Substances	Inflammasomes ; NLR Family, Pyrin Domain-Containing 3 Protein ; Adenosine Triphosphate (8L70Q75FXE) ; Adenosine (K72T3FS567)
Language	English
Publishing date	2021-01-29
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2020.603942
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Article ; Online: Hematopoiesis and innate immunity: an inseparable couple for good and bad times, bound together by an hormetic relationship.

Ratajczak, Mariusz Z / Kucia, Magdalena

Leukemia

2021 Volume 36, Issue 1, Page(s) 23–32

Abstract: Hematopoietic and immune cells originate from a common hematopoietic/lymphopoietic stem cell what explains that these different cell types often share the same receptors and respond to similar factors. Moreover, the common goal of both lineages is to ... ...

Abstract	Hematopoietic and immune cells originate from a common hematopoietic/lymphopoietic stem cell what explains that these different cell types often share the same receptors and respond to similar factors. Moreover, the common goal of both lineages is to ensure tissue homeostasis under steady-state conditions, fight invading pathogens, and promote tissue repair. We will highlight accumulating evidence that innate and adaptive immunity modulate several aspects of hematopoiesis within the hormetic zone in which the biological response to low exposure to potential stressors generally is favorable and benefits hematopoietic stem/progenitor cells (HSPCs). Innate immunity impact on hematopoiesis is pleiotropic and involves both the cellular arm, comprised of innate immunity cells, and the soluble arm, whose major component is the complement cascade (ComC). In addition, several mediators released by innate immunity cells, including inflammatory cytokines and small antimicrobial cationic peptides, affect hematopoiesis. There are intriguing observations that HSPCs and immune cells share several cell-surface pattern-recognition receptors (PRRs), such as Toll-like receptors (TLRs) and cytosol-expressed NOD, NOD-like, and RIG-I-like receptors and thus can be considered "pathogen sensors". In addition, not only lymphocytes but also HSPCs express functional intracellular complement proteins, defined as complosome which poses challenging questions for further investigation of the intracellular ComC-mediated intracrine regulation of hematopoiesis.
MeSH term(s)	Animals ; Hematopoiesis ; Humans ; Immunity, Innate ; Signal Transduction
Language	English
Publishing date	2021-12-01
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	807030-1
ISSN	1476-5551 ; 0887-6924
ISSN (online)	1476-5551
ISSN	0887-6924
DOI	10.1038/s41375-021-01482-0
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Zs.A 2295: Show issues

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Article ; Online: The Nlrp3 inflammasome - the evolving story of its positive and negative effects on hematopoiesis.

Ratajczak, Mariusz Z / Kucia, Magdalena

Current opinion in hematology

2021 Volume 28, Issue 4, Page(s) 251–261

Abstract: Purpose of review: Hematopoiesis is co-regulated by innate immunity, which is an ancient evolutionary defense mechanism also involved in the development and regeneration of damaged tissues. This review seeks to shed more light on the workings of the ... ...

Abstract	Purpose of review: Hematopoiesis is co-regulated by innate immunity, which is an ancient evolutionary defense mechanism also involved in the development and regeneration of damaged tissues. This review seeks to shed more light on the workings of the Nlrp3 inflammasome, which is an intracellular innate immunity pattern recognition receptor and sensor of changes in the hematopoietic microenvironment, and focus on its role in hematopoieisis. Recent findings: Hematopoietic stem progenitor cells (HSPCs) are exposed to several external mediators of innate immunity. Moreover, since hemato/lymphopoietic cells develop from a common stem cell, their behavior and fate are coregulated by intracellular innate immunity pathways. Therefore, the Nlrp3 inflammasome is functional both in immune cells and in HSPCs and affects hematopoiesis in either a positive or negative way, depending on its activity level. Specifically, while a physiological level of activation regulates the trafficking of HSPCs and most likely maintains their pool in the bone marrow, hyperactivation may lead to irreversible cell damage by pyroptosis and HSPC senescence and contribute to the origination of myelodysplasia and hematopoietic malignancies. Summary: Modulation of the level of Nrp3 inflammasome activation will enable improvements in HSPC mobilization, homing, and engraftment strategies. It may also control pathological activation of this protein complex during HSPC senescence, graft-versus-host disease, the induction of cytokine storms, and the development of hematopoietic malignancies.
MeSH term(s)	Animals ; Disease Susceptibility ; Gene Expression Regulation ; Hematopoiesis ; Hematopoietic Stem Cells/cytology ; Hematopoietic Stem Cells/metabolism ; Host-Pathogen Interactions/genetics ; Host-Pathogen Interactions/immunology ; Humans ; Immunity, Innate ; Inflammasomes/metabolism ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism ; Receptors, Pattern Recognition/metabolism ; Signal Transduction
Chemical Substances	Inflammasomes ; NLR Family, Pyrin Domain-Containing 3 Protein ; NLRP3 protein, human ; Receptors, Pattern Recognition
Language	English
Publishing date	2021-04-19
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1153887-9
ISSN	1531-7048 ; 1065-6251
ISSN (online)	1531-7048
ISSN	1065-6251
DOI	10.1097/MOH.0000000000000658
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Zs.A 3703: Show issues

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Article ; Online: Prerequisite Delivery Method and Academic Outcomes in a Physician Assistant Education Program.

Chalupa, Robyn L / Nevels, Torrance L / Kucia, Margaret M / Jones, James J

The journal of physician assistant education : the official journal of the Physician Assistant Education Association

2023 Volume 34, Issue 4, Page(s) 334–338

Abstract: Purpose: The Interservice Physician Assistant Program (IPAP) educates up to 169 matriculants per year. Each service branch sets the admission criteria, including all prerequisites, for their applicants. We hypothesized that prerequisites obtained online/ ...

Abstract	Purpose: The Interservice Physician Assistant Program (IPAP) educates up to 169 matriculants per year. Each service branch sets the admission criteria, including all prerequisites, for their applicants. We hypothesized that prerequisites obtained online/virtual are less rigorous than coursework completed in-person. The purpose of this investigation was to evaluate whether online/virtual prerequisite courses were associated with academic deceleration or attrition at any point. Methods: Student self-reported data were retrospectively analyzed to evaluate program scores of students who took prerequisites online/virtual or in-person. Results: There were no statistically significant differences in foundational course performance between online/virtual and in-person coursework. In addition, students who took anatomy online performed better than students who completed the coursework in-person (140.6 ± 15.6 vs. 145.6 ± 14.7, P = .05). Conclusions: This analysis indicates that using the prerequisite source to predict academic difficulty may not be possible in IPAP students. Faculty will need to continue to search for other predictors of academic difficulty.
MeSH term(s)	Humans ; School Admission Criteria ; Retrospective Studies ; Physician Assistants/education ; Students ; Faculty
Language	English
Publishing date	2023-09-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	2620682-1
ISSN	1941-9449 ; 1941-9430
ISSN (online)	1941-9449
ISSN	1941-9430
DOI	10.1097/JPA.0000000000000542
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Article ; Online: Hematopoiesis Revolves Around the Primordial Evolutional Rhythm of Purinergic Signaling and Innate Immunity - A Journey to the Developmental Roots.

Ratajczak, Mariusz Z / Bujko, Kamila / Brzezniakiewicz-Janus, Katarzyna / Ratajczak, Janina / Kucia, Magdalena

Stem cell reviews and reports

2024 Volume 20, Issue 3, Page(s) 827–838

Abstract: A cell's most significant existential task is to survive by ensuring proper metabolism, avoiding harmful stimuli, and adapting to changing environments. It explains why early evolutionary primordial signals and pathways remained active and regulate cell ... ...

Abstract	A cell's most significant existential task is to survive by ensuring proper metabolism, avoiding harmful stimuli, and adapting to changing environments. It explains why early evolutionary primordial signals and pathways remained active and regulate cell and tissue integrity. This requires energy supply and a balanced redox state. To meet these requirements, the universal intracellular energy transporter purine nucleotide-adenosine triphosphate (ATP) became an important signaling molecule and precursor of purinergic signaling after being released into extracellular space. Similarly, ancient proteins involved in intracellular metabolism gave rise to the third protein component (C3) of the complement cascade (ComC), a soluble arm of innate immunity. These pathways induce cytosol reactive oxygen (ROS) and reactive nitrogen species (RNS) that regulate the redox state of the cells. While low levels of ROS and RNS promote cell growth and differentiation, supra-physiological concentrations can lead to cell damage by pyroptosis. This balance explains the impact of purinergic signaling and innate immunity on cell metabolism, organogenesis, and tissue development. Subsequently, along with evolution, new regulatory cues emerge in the form of growth factors, cytokines, chemokines, and bioactive lipids. However, their expression is still modulated by both primordial signaling pathways. This review will focus on the data that purinergic signaling and innate immunity carry on their ancient developmental task in hematopoiesis and specification of hematopoietic stem/progenitor cells (HSPCs). Moreover, recent evidence shows both these regulatory pathways operate in a paracrine manner and inside HSPCs at the autocrine level.
MeSH term(s)	Reactive Oxygen Species/metabolism ; Immunity, Innate ; Hematopoietic Stem Cells ; Complement Activation ; Hematopoiesis
Chemical Substances	Reactive Oxygen Species
Language	English
Publishing date	2024-02-16
Publishing country	United States
Document type	Review ; Journal Article
ZDB-ID	2495577-2
ISSN	2629-3277 ; 1558-6804 ; 1550-8943
ISSN (online)	2629-3277 ; 1558-6804
ISSN	1550-8943
DOI	10.1007/s12015-024-10692-9
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Zs.A 6198: Show issues

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Article ; Online: Murine and Human-Purified very Small Embryonic-like Stem Cells (VSELs) Express Purinergic Receptors and Migrate to Extracellular ATP Gradient.

Bujko, Kamila / Brzezniakiewicz-Janus, Katarzyna / Jarczak, Justyna / Kucia, Magdalena / Ratajczak, Mariusz Z

Stem cell reviews and reports

2024

Abstract: Purinergic signaling is an ancient primordial signaling system regulating tissue development and specification of various types of stem cells. Thus, functional purinergic receptors are present in several types of cells in the body, including multiple ... ...

Abstract	Purinergic signaling is an ancient primordial signaling system regulating tissue development and specification of various types of stem cells. Thus, functional purinergic receptors are present in several types of cells in the body, including multiple populations of stem cells. However, one stem cell type that has not been evaluated for expression of purinergic receptors is very small embryonic stem cells (VSELs) isolated from postnatal tissues. Herein, we report that human umbilical cord blood (UCB) and murine bone marrow (BM) purified VSELs express mRNA for P1 and P2 purinergic receptors and CD39 and CD73 ectonucleotidases converting extracellular ATP (eATP) into its signaling metabolite extracellular adenosine (eAdo), that antagonizes eATP effects. More importantly, we demonstrate that human and murine VSELs respond by chemotaxis to eATP, and eAdo inhibits this migration. These responses to eATP are mediated by activation of Nlrp3 inflammasome, and exposure of VSELs to its specific inhibitor MCC950 abolished the chemotactic response to ATP. We conclude that purinergic signaling plays an essential, underappreciated role in the biology of these cells and their potential role in response to tissue/organ injuries.
Language	English
Publishing date	2024-04-18
Publishing country	United States
Document type	Journal Article
ZDB-ID	2495577-2
ISSN	2629-3277 ; 1558-6804 ; 1550-8943
ISSN (online)	2629-3277 ; 1558-6804
ISSN	1550-8943
DOI	10.1007/s12015-024-10716-4
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Zs.A 6198: Show issues

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Article ; Online: External Liver-Derived Complement and Intrinsic Present in Hematopoietic Stem/Progenitor Cells Complosome Modulate Cell Metabolism and Response to Stress.

Thapa, Arjun / Ratajczak, Janina / Kucia, Magdalena / Ratajczak, Mariusz Z

Stem cell reviews and reports

2023 Volume 19, Issue 5, Page(s) 1177–1184

Abstract: Hematopoietic stem/progenitor cells (HSPCs) express receptors for complement cascade (ComC) cleavage fragments C3a and C5a and may respond to inflammation-related cues by sensing pathogen-associated molecular pattern molecules (PAMPs) released by ... ...

Abstract	Hematopoietic stem/progenitor cells (HSPCs) express receptors for complement cascade (ComC) cleavage fragments C3a and C5a and may respond to inflammation-related cues by sensing pathogen-associated molecular pattern molecules (PAMPs) released by pathogens as well as non-infectious danger associated molecular pattern molecules (DAMPs) or alarmin generated during stress/tissue damage sterile inflammation. To facilitate this HSPCs are equipped with C3a and C5a receptors, C3aR and C5aR, respectively, and express on the outer cell membrane and in cytosol pattern recognition receptors (PPRs) that sense PAMPs and DAMPs. Overall, danger-sensing mechanisms in HSPCs mimic those seen in immune cells, which should not surprise as hematopoiesis and the immune system develop from the same common stem cell precursor. This review will focus on the role of ComC-derived C3a and C5a that trigger nitric oxide synthetase-2 (Nox2) complex to release reactive oxygen species (ROS) that activate important cytosolic PRRs-Nlrp3 inflammasome, which orchestrates responsiveness of HSPCs to stress. Moreover, recent data indicate that in addition to circulating in peripheral blood (PB) activated liver-derived ComC proteins, a similar role plays ComC expressed and intrinsically activated in HSPCs known as "complosome". We postulate that ComC triggered Nox2-ROS-Nlrp3 inflammasome responses, if they occur within non-toxic to cells' "hormetic range of activation", positively regulate HSCs migration, metabolism, and proliferation. This sheds a new light on the immune-metabolic regulation of hematopoiesis.
MeSH term(s)	Humans ; Inflammasomes/metabolism ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism ; Pathogen-Associated Molecular Pattern Molecules/metabolism ; Reactive Oxygen Species/metabolism ; Hematopoietic Stem Cells/metabolism ; Complement System Proteins/metabolism ; Inflammation/metabolism ; Liver/metabolism
Chemical Substances	Inflammasomes ; NLR Family, Pyrin Domain-Containing 3 Protein ; Pathogen-Associated Molecular Pattern Molecules ; Reactive Oxygen Species ; Complement System Proteins (9007-36-7)
Language	English
Publishing date	2023-03-28
Publishing country	United States
Document type	Journal Article ; Review ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2495577-2
ISSN	2629-3277 ; 1558-6804 ; 1550-8943
ISSN (online)	2629-3277 ; 1558-6804
ISSN	1550-8943
DOI	10.1007/s12015-023-10533-1
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