Article (Scientific journals)
Single and combined impacts of irradiation and surgery on lymphatic vasculature and fibrosis associated to secondary lymphedema
Buntinx, Florence; Lebeau, Alizée; Gillot, Lionel et al.
2022In Frontiers in Pharmacology, 13
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Keywords :
Pharmacology (medical); Pharmacology
Abstract :
[en] Lymphedema (LD) refers to a condition of lymphatic dysfunction associated with excessive fluid accumulation, fibroadipose tissue deposition and swelling. In industrialized countries, LD development mainly results from a local disruption of the lymphatic network by an infection or cancer-related surgery (secondary LD). In the absence of efficient therapy, animal models are needed to decipher the cellular and molecular mechanisms underlying LD and test putative drugs. In this study, we optimized and characterized a murine model of LD that combines an irradiation of the mice hind limb and a radical surgery (lymph node resection associated to lymphatic vessel ligation). We investigated the respective roles of irradiation and surgery in LD formation by comparing their impacts, alone or in combination (with different intervention sequences), on eight different features of the pathology: swelling (paw thickness), indocyanine green (ICG) clearance, lymphatic vasculature remodeling, epidermal and dermal thickening, adipocyte accumulation, inflammatory cell infiltration and collagen deposition. This study supports the importance of radiation prior to surgery to experimentally induce a rapid, severe and sustained tissue remodeling harboring the different hallmarks of LD. We provide the first experimental evidence for an excessive deposition of periostin (POSTN) and tenascin-C (TNC) in LD. Through a computerized method of digital image quantification, we established the spatial map of lymphatic expansion, as well as collagen, POSTN and TNC deposition in papillary and reticular dermis of lymphedematous skins. This mouse model is available to study the patho-physiology of LD and test potential therapeutic targets.
Disciplines :
Laboratory medicine & medical technology
Author, co-author :
Buntinx, Florence   ;  Université de Liège - ULiège > Département des sciences cliniques > Labo de biologie des tumeurs et du développement
Lebeau, Alizée  ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biologie cellulaire et moléculaire
Gillot, Lionel ;  Université de Liège - ULiège > GIGA > GIGA Cancer - Tumours and development biology
Baudin, Louis ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biologie cellulaire et moléculaire
Ndong Penda, R.
Morfoisse, F.
LALLEMAND, François  ;  Centre Hospitalier Universitaire de Liège - CHU > > Service médical de radiothérapie
Vottero, G.
NIZET, Christophe ;  Centre Hospitalier Universitaire de Liège - CHU > > Service de chirurgie plastique et maxillo-faciale
Nizet, Jean-Luc ;  Centre Hospitalier Universitaire de Liège - CHU > > Service de chirurgie plastique et maxillo-faciale
Blacher, Silvia ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biologie cellulaire et moléculaire
Noël, Agnès ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biologie cellulaire et moléculaire
 These authors have contributed equally to this work.
Language :
English
Title :
Single and combined impacts of irradiation and surgery on lymphatic vasculature and fibrosis associated to secondary lymphedema
Publication date :
18 October 2022
Journal title :
Frontiers in Pharmacology
ISSN :
1663-9812
Publisher :
Frontiers Media SA
Volume :
13
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 21 November 2022

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