Lymphatic MAFB regulates vascular patterning during developmental and pathological lymphangiogenesis.

Dieterich, Lothar C; Tacconi, Carlotta; Menzi, Franziska; Proulx, Steven T; Kapaklikaya, Kübra; Hamada, Michito; Takahashi, Satoru; Detmar, Michael (2020). Lymphatic MAFB regulates vascular patterning during developmental and pathological lymphangiogenesis. Angiogenesis, 23(3), pp. 411-423. Springer Netherlands 10.1007/s10456-020-09721-1

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MAFB is a transcription factor involved in the terminal differentiation of several cell types, including macrophages and keratinocytes. MAFB is also expressed in lymphatic endothelial cells (LECs) and is upregulated by VEGF-C/VEGFR-3 signaling. Recent studies have revealed that MAFB regulates several genes involved in lymphatic differentiation and that global Mafb knockout mice show defects in patterning of lymphatic vessels during embryogenesis. However, it has remained unknown whether this effect is LEC-intrinsic and whether MAFB might also be involved in postnatal lymphangiogenesis. We established conditional, lymphatic-specific Mafb knockout mice and found comparable lymphatic patterning defects during embryogenesis as in the global MAFB knockout. Lymphatic MAFB deficiency resulted in increased lymphatic branching in the diaphragm at P7, but had no major effect on lymphatic patterning or function in healthy adult mice. By contrast, tumor-induced lymphangiogenesis was enhanced in mice lacking lymphatic MAFB. Together, these data reveal that LEC-expressed MAFB is involved in lymphatic vascular morphogenesis during embryonic and postnatal development as well as in pathological conditions. Therefore, MAFB could represent a target for therapeutic modulation of lymphangiogenesis.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Theodor Kocher Institute

UniBE Contributor:

Proulx, Steven Thomas

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

0969-6970

Publisher:

Springer Netherlands

Language:

English

Submitter:

Ursula Zingg-Zünd

Date Deposited:

25 Jan 2021 11:45

Last Modified:

10 Mar 2021 15:32

Publisher DOI:

10.1007/s10456-020-09721-1

PubMed ID:

32307629

Uncontrolled Keywords:

Branching Lymphangiogenesis Postnatal development Transcription factor Vascular morphogenesis

BORIS DOI:

10.48350/150923

URI:

https://boris.unibe.ch/id/eprint/150923

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