eprintid: 31721
rev_number: 15
eprint_status: archive
userid: 6739
dir: disk0/00/03/17/21
datestamp: 2022-06-14 11:44:04
lastmod: 2022-06-21 16:07:41
status_changed: 2022-06-14 11:44:04
type: doctoralThesis
metadata_visibility: show
creators_name: Künzel, Steffen Emil
title: NCK1/2 are specific mediators of migration in Pericytes and promising targets in ischemic retinopathies
subjects: ddc-610
divisions: i-63600
adv_faculty: af-06
abstract: The particular focus of my dissertation is on pericytes which are mural cells that surround capillaries and control angiogenesis and capillary barrier function. I investigate endothelial cell-derived platelet-derived growth factor-B (PDGF-B) signaling during sprouting angiogenesis in health and disease. With this, I show that “activated” α-SMA-expressing pericytes cover angiogenic sprouts and pathological neovascular tufts (NVTs) in a mouse model of oxygen-induced retinopathy. By genetic lineage tracing experiments, this work demonstrates that pericytes acquire α-SMA expression during pathological NVT formation. Pericyte depletion through inducible endothelial-specific knockout of the ligand Pdgf-b decreases this NVT formation, but also impairs revascularization. Moreover, I demonstrate that loss of Nck1 and Nck2 in mural cells prevents NVT formation and vascular leakage and promotes revascularization, suggesting NCK signaling as a potential target for the treatment of retinopathies.
date: 2022
id_scheme: DOI
id_number: 10.11588/heidok.00031721
ppn_swb: 1807389499
own_urn: urn:nbn:de:bsz:16-heidok-317211
date_accepted: 2022-03-10
advisor: HASH(0x55de57aeb840)
language: eng
bibsort: KUNZELSTEFNCK12ARESP2022
full_text_status: public
place_of_pub: Heidelberg
citation:   Künzel, Steffen Emil  (2022) NCK1/2 are specific mediators of migration in Pericytes and promising targets in ischemic retinopathies.  [Dissertation]     
document_url: https://archiv.ub.uni-heidelberg.de/volltextserver/31721/1/Dissertation_SteffenEKuenzel_2022.pdf