Universität zu Köln

Hatami, Niloofar, Buettner, Christian, Bock, Felix, Simfors, Sara, Musial, Gwen, Reis, Andre, Cursiefen, Claus and Clahsen, Thomas (2022). Cystathionine beta-synthase as novel endogenous regulator of lymphangiogenesis via modulating VEGF receptor 2 and 3. Commun. Biol., 5 (1). BERLIN: NATURE PORTFOLIO. ISSN 2399-3642

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Abstract

Lymphangiogenesis is a key player in several diseases such as tumor metastasis, obesity, and graft rejection. Endogenous regulation of lymphangiogenesis is only partly understood. Here we use the normally avascular cornea as a model to identify endogenous regulators of lymphangiogenesis. Quantitative trait locus analysis of a large low-lymphangiogenic BALB/cN x high-lymphangiogenic C57BL/6 N intercross and prioritization by whole-transcriptome sequencing identify a novel gene responsible for differences in lymphatic vessel architecture on chromosome 17, the cystathionine beta-synthase (Cbs). Inhibition of CBS in lymphatic endothelial cells results in reduce proliferation, migration, altered tube-formation, and decrease expression of vascular endothelial growth factor (VEGF) receptor 2 (VEGF-R2) and VEGF-R3, but not their ligands VEGF-C and VEGF-D. Also in vivo inflammation-induced lymphangiogenesis is significantly reduce in C57BL/6 N mice after pharmacological inhibition of CBS. The results confirm CBS as a novel endogenous regulator of lymphangiogenesis acting via VEGF receptor 2 and 3-regulation and open new treatment avenues in diseases associated with pathologic lymphangiogenesis. Quantitative trait locus analysis of BALB/cN x C57BL/6 N intercross identifies cystathionine beta-synthase as a previously unknown regulator of lymphangiogenesis by affecting VEGF-R2/VEGF-R3 expression in lymphatic endothelial cells.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Hatami, Niloofar UNSPECIFIED UNSPECIFIED UNSPECIFIED Buettner, Christian UNSPECIFIED UNSPECIFIED UNSPECIFIED Bock, Felix UNSPECIFIED UNSPECIFIED UNSPECIFIED Simfors, Sara UNSPECIFIED UNSPECIFIED UNSPECIFIED Musial, Gwen UNSPECIFIED UNSPECIFIED UNSPECIFIED Reis, Andre UNSPECIFIED UNSPECIFIED UNSPECIFIED Cursiefen, Claus UNSPECIFIED UNSPECIFIED UNSPECIFIED Clahsen, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-669071
DOI:	10.1038/s42003-022-03923-7
Journal or Publication Title:	Commun. Biol.
Volume:	5
Number:	1
Date:	2022
Publisher:	NATURE PORTFOLIO
Place of Publication:	BERLIN
ISSN:	2399-3642
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CORNEAL LYMPHANGIOGENESIS; CELL-PROLIFERATION; HYDROGEN-SULFIDE; ANGIOGENESIS; MECHANISMS; INHIBITION; MODEL; VASCULATURE; METABOLISM; EXPRESSION Multiple languages Biology; Multidisciplinary Sciences Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/66907