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Microbiota-Derived Propionate Modulates Megakaryopoiesis and Platelet Function
Rheumatoid arthritis (RA) is associated with an increased risk for cardiovascular events driven by abnormal platelet clotting effects. Platelets are produced by megakaryocytes, deriving from megakaryocyte erythrocyte progenitors (MEP) in the bone marrow. Increased megakaryocyte expansion across comm...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9307893/ https://www.ncbi.nlm.nih.gov/pubmed/35880182 http://dx.doi.org/10.3389/fimmu.2022.908174 |
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author | Dürholz, Kerstin Schmid, Eva Frech, Michael Azizov, Vugar Otterbein, Nadine Lucas, Sébastien Rauh, Manfred Schett, Georg Bruns, Heiko Zaiss, Mario M. |
author_facet | Dürholz, Kerstin Schmid, Eva Frech, Michael Azizov, Vugar Otterbein, Nadine Lucas, Sébastien Rauh, Manfred Schett, Georg Bruns, Heiko Zaiss, Mario M. |
author_sort | Dürholz, Kerstin |
collection | PubMed |
description | Rheumatoid arthritis (RA) is associated with an increased risk for cardiovascular events driven by abnormal platelet clotting effects. Platelets are produced by megakaryocytes, deriving from megakaryocyte erythrocyte progenitors (MEP) in the bone marrow. Increased megakaryocyte expansion across common autoimmune diseases was shown for RA, systemic lupus erythematosus (SLE) and primary Sjögren’s syndrome (pSS). In this context, we evaluated the role of the microbial-derived short chain fatty acid (SCFA) propionate on hematopoietic progenitors in the collagen induced inflammatory arthritis model (CIA) as we recently showed attenuating effects of preventive propionate treatment on CIA severity. In vivo, propionate treatment starting 21 days post immunization (dpi) reduced the frequency of MEPs in the bone marrow of CIA and naïve mice. Megakaryocytes numbers were reduced but increased the expression of the maturation marker CD61. Consistent with this, functional analysis of platelets showed an upregulated reactivity state following propionate-treatment. This was confirmed by elevated histone 3 acetylation and propionylation as well as by RNAseq analysis in Meg-01 cells. Taken together, we identified a novel nutritional axis that skews platelet formation and function. |
format | Online Article Text |
id | pubmed-9307893 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-93078932022-07-24 Microbiota-Derived Propionate Modulates Megakaryopoiesis and Platelet Function Dürholz, Kerstin Schmid, Eva Frech, Michael Azizov, Vugar Otterbein, Nadine Lucas, Sébastien Rauh, Manfred Schett, Georg Bruns, Heiko Zaiss, Mario M. Front Immunol Immunology Rheumatoid arthritis (RA) is associated with an increased risk for cardiovascular events driven by abnormal platelet clotting effects. Platelets are produced by megakaryocytes, deriving from megakaryocyte erythrocyte progenitors (MEP) in the bone marrow. Increased megakaryocyte expansion across common autoimmune diseases was shown for RA, systemic lupus erythematosus (SLE) and primary Sjögren’s syndrome (pSS). In this context, we evaluated the role of the microbial-derived short chain fatty acid (SCFA) propionate on hematopoietic progenitors in the collagen induced inflammatory arthritis model (CIA) as we recently showed attenuating effects of preventive propionate treatment on CIA severity. In vivo, propionate treatment starting 21 days post immunization (dpi) reduced the frequency of MEPs in the bone marrow of CIA and naïve mice. Megakaryocytes numbers were reduced but increased the expression of the maturation marker CD61. Consistent with this, functional analysis of platelets showed an upregulated reactivity state following propionate-treatment. This was confirmed by elevated histone 3 acetylation and propionylation as well as by RNAseq analysis in Meg-01 cells. Taken together, we identified a novel nutritional axis that skews platelet formation and function. Frontiers Media S.A. 2022-07-08 /pmc/articles/PMC9307893/ /pubmed/35880182 http://dx.doi.org/10.3389/fimmu.2022.908174 Text en Copyright © 2022 Dürholz, Schmid, Frech, Azizov, Otterbein, Lucas, Rauh, Schett, Bruns and Zaiss https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Dürholz, Kerstin Schmid, Eva Frech, Michael Azizov, Vugar Otterbein, Nadine Lucas, Sébastien Rauh, Manfred Schett, Georg Bruns, Heiko Zaiss, Mario M. Microbiota-Derived Propionate Modulates Megakaryopoiesis and Platelet Function |
title | Microbiota-Derived Propionate Modulates Megakaryopoiesis and Platelet Function |
title_full | Microbiota-Derived Propionate Modulates Megakaryopoiesis and Platelet Function |
title_fullStr | Microbiota-Derived Propionate Modulates Megakaryopoiesis and Platelet Function |
title_full_unstemmed | Microbiota-Derived Propionate Modulates Megakaryopoiesis and Platelet Function |
title_short | Microbiota-Derived Propionate Modulates Megakaryopoiesis and Platelet Function |
title_sort | microbiota-derived propionate modulates megakaryopoiesis and platelet function |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9307893/ https://www.ncbi.nlm.nih.gov/pubmed/35880182 http://dx.doi.org/10.3389/fimmu.2022.908174 |
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