Identification of myeloid-derived growth factor as a mechanically-induced, growth-promoting angiocrine signal for human hepatocytes

Linda Große-Segerath, Paula Follert, Kristina Behnke, Julia Ettich, Tobias Buschmann, Philip Kirschner, Sonja Hartwig, Stefan Lehr, Mortimer Korf-Klingebiel, Daniel Eberhard, Nadja Lehwald-Tywuschik, Hadi Al-Hasani, Wolfram Trudo Knoefel, Stefan Heinrich, Bodo Levkau, Kai C. Wollert, Jürgen Scheller and Eckhard Lammert ()
Additional contact information
Linda Große-Segerath: Heinrich Heine University Düsseldorf, Faculty of Mathematics and Natural Sciences, Institute of Metabolic Physiology
Paula Follert: Heinrich Heine University Düsseldorf, Faculty of Mathematics and Natural Sciences, Institute of Metabolic Physiology
Kristina Behnke: Heinrich Heine University Düsseldorf
Julia Ettich: Heinrich Heine University Düsseldorf
Tobias Buschmann: Heinrich Heine University Düsseldorf
Philip Kirschner: Heinrich Heine University Düsseldorf, Faculty of Mathematics and Natural Sciences, Institute of Metabolic Physiology
Sonja Hartwig: German Center for Diabetes Research (DZD e.V.), Helmholtz Zentrum München
Stefan Lehr: German Center for Diabetes Research (DZD e.V.), Helmholtz Zentrum München
Mortimer Korf-Klingebiel: Hannover Medical School
Daniel Eberhard: Heinrich Heine University Düsseldorf, Faculty of Mathematics and Natural Sciences, Institute of Metabolic Physiology
Nadja Lehwald-Tywuschik: Heinrich Heine University Düsseldorf
Hadi Al-Hasani: German Center for Diabetes Research (DZD e.V.), Helmholtz Zentrum München
Wolfram Trudo Knoefel: Heinrich Heine University Düsseldorf
Stefan Heinrich: University Hospital Center Mainz
Bodo Levkau: Heinrich Heine University Düsseldorf
Kai C. Wollert: Hannover Medical School
Jürgen Scheller: Heinrich Heine University Düsseldorf
Eckhard Lammert: Heinrich Heine University Düsseldorf, Faculty of Mathematics and Natural Sciences, Institute of Metabolic Physiology

Nature Communications, 2024, vol. 15, issue 1, 1-15

Abstract: Abstract Recently, we have shown that after partial hepatectomy (PHx), an increased hepatic blood flow initiates liver growth in mice by vasodilation and mechanically-triggered release of angiocrine signals. Here, we use mass spectrometry to identify a mechanically-induced angiocrine signal in human hepatic endothelial cells, that is, myeloid-derived growth factor (MYDGF). We show that it induces proliferation and promotes survival of primary human hepatocytes derived from different donors in two-dimensional cell culture, via activation of mitogen-activated protein kinase (MAPK) and signal transducer and activator of transcription 3 (STAT3). MYDGF also enhances proliferation of human hepatocytes in three-dimensional organoids. In vivo, genetic deletion of MYDGF decreases hepatocyte proliferation in the regenerating mouse liver after PHx; conversely, adeno-associated viral delivery of MYDGF increases hepatocyte proliferation and MAPK signaling after PHx. We conclude that MYDGF represents a mechanically-induced angiocrine signal and that it triggers growth of, and provides protection to, primary mouse and human hepatocytes.

Date: 2024
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-024-44760-y Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-44760-y

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-024-44760-y

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().