Universität zu Köln

Hatami, Niloofar (2026). Identification of Novel Endogenous Modulators of (Inflammatory) Lymphangiogenesis by Analyzing Mouse Strain-specific Differences. PhD thesis, Universität zu Köln.

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Abstract

This thesis investigates the role of novel endogenous modulators in lymphangiogenesis, with a focus on analysing mouse strain-specific differences. Understanding lymphangiogenesis is crucial due to its implications for immune responses, fluid balance, and various pathological conditions, including cancer metastasis and inflammatory diseases. This study aims to provide insights into the molecular mechanisms that regulate lymphangiogenesis, which could inform therapeutic strategies for conditions involving aberrant lymphatic vessel formation. The research employed a combination of in vitro and in vivo experimental approaches. Human dermal lymphatic endothelial cells (HDLECs) were utilized to assess the effects of cystathionine β-synthase (CBS) and angiopoietin-like 4 (ANGPTL4) on lymphangiogenesis. Various assays, including proliferation, apoptosis, migration, and tube formation assays, were conducted to evaluate the impact of these proteins on lymphangiogenesis. For the study of Angptl4, knockout mice were used to understand its role in lymphatic vessel formation. Additionally, in vivo models involving different mouse strains (C57BL/6 and BALB/c) were employed to analyze inflammatory lymphangiogenesis via suture-induced corneal neovascularization assays. To identify additional novel modulators of lymphangiogenesis, naïve eyes from different Collaborative Cross (CC) lines were obtained, and whole-mount cornea staining was performed using LYVE-1 to analyze lymphatic vessel formation. Furthermore, 8- to 12-week-old male and female BOON_HF and NUK_AC mice were used for the suture-induced inflammatory corneal neovascularization assay for CC line mice. The study identified CBS and ANGPTL4 as significant regulators of lymphangiogenesis. Investigation of CBS revealed its impact on the proliferation and migration of HDLECs, as well as its influence on the expression of lymphangiogenic factors, including VEGFR-2 and VEGFR-3. Furthermore, ANGPTL4 has been shown to affect lymphatic vessel formation, with knockout models demonstrating an increased lymphatic surface area compared to their wild-type counterparts. Genetic analysis within the CC lines highlighted strain-dependent differences in lymphangiogenic responses, establishing a link between genetic background and lymphangiogenic potential. This investigation establishes CBS and ANGPTL4 as novel regulators of lymphangiogenesis, highlighting their potential role in modulating lymphatic responses. Furthermore, this research contributes to the understanding of endogenous modulators of lymphangiogenesis, highlighting the potential of the Collaborative Cross (CC) project in identifying additional novel regulators, thereby paving the way for therapeutic interventions in diseases associated with abnormal lymphatic vessel growth.

Item Type:	Thesis (PhD thesis)
Creators:	Creators Email ORCID ORCID Put Code Hatami, Niloofar nhatami2@smail.uni-koeln.de UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-798081
Date:	2026
Language:	English
Faculty:	Faculty of Mathematics and Natural Sciences
Divisions:	Faculty of Mathematics and Natural Sciences > Department of Mathematics and Science Education > Institute of Biology Education
Subjects:	Natural sciences and mathematics
Uncontrolled Keywords:	Keywords Language Corneal disease English Lymphangiogenesis English Cancer English
Date of oral exam:	27 January 2026
Referee:	Name Academic Title Cursiefen, Claus Univ.-Prof. Dr.
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/79808