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Mouse liver injury induces hepatic macrophage FGF23 production
Fibroblast growth factor 23 (FGF23) is a bone marrow cell produced hormone that functions in the intestine and kidney to regulate phosphate homeostasis. Increased serum FGF23 is a well-established predictor of mortality in renal disease, but recent findings linking increased levels to hepatic and ca...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8887750/ https://www.ncbi.nlm.nih.gov/pubmed/35231062 http://dx.doi.org/10.1371/journal.pone.0264743 |
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author | Kumar, Pradeep Liu, Yunshan Shen, Yang Maher, Jacquelyn J. Cingolani, Francesca Czaja, Mark J. |
author_facet | Kumar, Pradeep Liu, Yunshan Shen, Yang Maher, Jacquelyn J. Cingolani, Francesca Czaja, Mark J. |
author_sort | Kumar, Pradeep |
collection | PubMed |
description | Fibroblast growth factor 23 (FGF23) is a bone marrow cell produced hormone that functions in the intestine and kidney to regulate phosphate homeostasis. Increased serum FGF23 is a well-established predictor of mortality in renal disease, but recent findings linking increased levels to hepatic and cardiac diseases have suggested that other organs are sources of FGF23 or targets of its effects. The potential ability of the liver to produce FGF23 in response to hepatocellular injury was therefore examined. Very low levels of Fgf23 mRNA and FGF23 protein were detected in normal mouse liver, but the amounts increased markedly during acute liver injury from the hepatotoxin carbon tetrachloride. Serum levels of intact FGF23 were elevated during liver injury from carbon tetrachloride. Chronic liver injury induced by a high fat diet or elevated bile acids also increased hepatic FGF23 levels. Stimulation of toll-like receptor (TLR) 4-driven inflammation by gut-derived lipopolysaccharide (LPS) underlies many forms of liver injury, and LPS induced Fgf23 in the liver as well as in other organs. The LPS-inducible cytokines IL-1β and TNF increased hepatic Fgf23 expression as did a TLR2 agonist Pam2CSK3. Analysis of Fgf23 expression and FGF23 secretion in different hepatic cell types involved in liver injury identified the resident liver macrophage or Kupffer cell as a source of hepatic FGF23. LPS and cytokines selectively induced the hormone in these cells but not in hepatocytes or hepatic stellate cells. FGF23 failed to exert any autocrine effect on the inflammatory state of Kupffer cells but did trigger proinflammatory activation of hepatocytes. During liver injury inflammatory factors induce Kupffer cell production of FGF23 that may have a paracrine proinflammatory effect on hepatocytes. Liver-produced FGF23 may have systemic hormonal effects as well that influence diseases in in other organs. |
format | Online Article Text |
id | pubmed-8887750 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-88877502022-03-02 Mouse liver injury induces hepatic macrophage FGF23 production Kumar, Pradeep Liu, Yunshan Shen, Yang Maher, Jacquelyn J. Cingolani, Francesca Czaja, Mark J. PLoS One Research Article Fibroblast growth factor 23 (FGF23) is a bone marrow cell produced hormone that functions in the intestine and kidney to regulate phosphate homeostasis. Increased serum FGF23 is a well-established predictor of mortality in renal disease, but recent findings linking increased levels to hepatic and cardiac diseases have suggested that other organs are sources of FGF23 or targets of its effects. The potential ability of the liver to produce FGF23 in response to hepatocellular injury was therefore examined. Very low levels of Fgf23 mRNA and FGF23 protein were detected in normal mouse liver, but the amounts increased markedly during acute liver injury from the hepatotoxin carbon tetrachloride. Serum levels of intact FGF23 were elevated during liver injury from carbon tetrachloride. Chronic liver injury induced by a high fat diet or elevated bile acids also increased hepatic FGF23 levels. Stimulation of toll-like receptor (TLR) 4-driven inflammation by gut-derived lipopolysaccharide (LPS) underlies many forms of liver injury, and LPS induced Fgf23 in the liver as well as in other organs. The LPS-inducible cytokines IL-1β and TNF increased hepatic Fgf23 expression as did a TLR2 agonist Pam2CSK3. Analysis of Fgf23 expression and FGF23 secretion in different hepatic cell types involved in liver injury identified the resident liver macrophage or Kupffer cell as a source of hepatic FGF23. LPS and cytokines selectively induced the hormone in these cells but not in hepatocytes or hepatic stellate cells. FGF23 failed to exert any autocrine effect on the inflammatory state of Kupffer cells but did trigger proinflammatory activation of hepatocytes. During liver injury inflammatory factors induce Kupffer cell production of FGF23 that may have a paracrine proinflammatory effect on hepatocytes. Liver-produced FGF23 may have systemic hormonal effects as well that influence diseases in in other organs. Public Library of Science 2022-03-01 /pmc/articles/PMC8887750/ /pubmed/35231062 http://dx.doi.org/10.1371/journal.pone.0264743 Text en © 2022 Kumar et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Kumar, Pradeep Liu, Yunshan Shen, Yang Maher, Jacquelyn J. Cingolani, Francesca Czaja, Mark J. Mouse liver injury induces hepatic macrophage FGF23 production |
title | Mouse liver injury induces hepatic macrophage FGF23 production |
title_full | Mouse liver injury induces hepatic macrophage FGF23 production |
title_fullStr | Mouse liver injury induces hepatic macrophage FGF23 production |
title_full_unstemmed | Mouse liver injury induces hepatic macrophage FGF23 production |
title_short | Mouse liver injury induces hepatic macrophage FGF23 production |
title_sort | mouse liver injury induces hepatic macrophage fgf23 production |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8887750/ https://www.ncbi.nlm.nih.gov/pubmed/35231062 http://dx.doi.org/10.1371/journal.pone.0264743 |
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