Journal Article

DKFZ-2017-01124

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Endothelial cell-derived angiopoietin-2 controls liver regeneration as a spatiotemporal rheostat.

Hu, J. (First author)DKFZ* ; Srivastava, K.DKFZ* ; Wieland, M.DKFZ* ; Runge, A.DKFZ* ; Mogler, C.DKFZ* ; Besemfelder, E.DKFZ* ; Terhardt, D.DKFZ* ; Vogel, M. J.DKFZ* ; Cao, L.DKFZ* ; Korn, C.DKFZ* ; Bartels, S.DKFZ* ; Thomas, M. ; Augustin, H. (Last author)DKFZ*

2014
American Association for the Advancement of Science38566 Washington, DC [u.a.]

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Please use a persistent id in citations: doi:10.1126/science.1244880

Abstract: Liver regeneration requires spatially and temporally precisely coordinated proliferation of the two major hepatic cell populations, hepatocytes and liver sinusoidal endothelial cells (LSECs), to reconstitute liver structure and function. The underlying mechanisms of this complex molecular cross-talk remain elusive. Here, we show that the expression of Angiopoietin-2 (Ang2) in LSECs is dynamically regulated after partial hepatectomy. During the early inductive phase of liver regeneration, Ang2 down-regulation leads to reduced LSEC transforming growth factor-β1 production, enabling hepatocyte proliferation by releasing an angiocrine proliferative brake. During the later angiogenic phase of liver regeneration, recovery of endothelial Ang2 expression enables regenerative angiogenesis by controlling LSEC vascular endothelial growth factor receptor 2 expression. The data establish LSECs as a dynamic rheostat of liver regeneration, spatiotemporally orchestrating hepatocyte and LSEC proliferation through angiocrine- and autocrine-acting Ang2, respectively.

Keyword(s): Angiopoietin-2 ; Transforming Growth Factor beta

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Contributing Institute(s):

1. Vaskuläre Onkologie und Metastasierung (A190)
2. Medizinische Physik in der Radiologie (E020)
3. Tumor- und Mikroumgebung (A101)
4. DKTK Heidelberg (L101)

Research Program(s):

1. 321 - Basic Concepts (POF3-321) (POF3-321)

Appears in the scientific report 2014

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Database coverage:
; BIOSIS Previews ; Current Contents - Agriculture, Biology and Environmental Sciences ; Current Contents - Life Sciences ; Current Contents - Physical, Chemical and Earth Sciences ; Ebsco Academic Search ; IF >= 30 ; JCR ; NCBI Molecular Biology Database ; National-Konsortium ; Nationallizenz ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Thomson Reuters Master Journal List ; Web of Science Core Collection ; Zoological Record

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