Impaired wound healing in mice lacking the basement membrane protein nidogen 1.
Nidogens 1 and 2 are ubiquitous basement membrane (BM) components, whose interactions in particular with laminin, collagen IV and perlecan have been considered important for BM formation. Genetic deletion of either NID gene does not reveal BM alterations suggesting compensatory roles for nidogens 1 and 2. However, neurological deficits in nidogen 1 null mice, not seen in the absence of nidogen 2, also suggest isoform specific functions. To test this further, skin wound healing which requires BM reformation was studied in adult nidogen 1 deficient mice. Although re-epithelialization was not altered, the newly formed epidermis showed marked hyperproliferation and a delay in differentiation at day 10 post injury. Distinct to control wounds, there was also considerable alpha-smooth muscle actin staining in the dermis of nidogen 1 deficient wounds at this time point. Further, laminin deposition and distribution of the beta1 and beta4 integrin chains were also significantly altered whereas the deposition of other BM components, including nidogen 2, was unchanged. Surprisingly, these differences between control and mutant wounds at day 10 post wounding did not affect the ultrastructural appearance of the dermo-epidermal BM suggesting a non-structural role for nidogen 1 in wound repair.
Baranowsky
Anke
A
Department of Dermatology, University Hospital Cologne, Cologne, Germany.
Mokkapati
Sharada
S
Bechtel
Manuela
M
Krügel
Jenny
J
Miosge
Nicolai
N
Wickenhauser
Claudia
C
Smyth
Neil
N
Nischt
Roswitha
R
D000818:Animals; D001485:Basement Membrane / Q000737:chemistry* / Q000378:metabolism; D002135:Calcium-Binding Proteins; D015815:Cell Adhesion Molecules; D002454:Cell Differentiation / Q000502:physiology; D024141:Collagen Type IV / Q000378:metabolism; D000078404:Epidermal Cells; D004817:Epidermis / Q000473:pathology / Q000502:physiology; D005260:Female; D006097:Granulation Tissue / Q000166:cytology / Q000378:metabolism; D016023:Integrins / Q000378:metabolism; D007365:Intercellular Junctions / Q000378:metabolism / Q000648:ultrastructure; D007797:Laminin / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D014945:Wound Healing / Q000502:physiology*
D002135:Calcium-Binding Proteins; D015815:Cell Adhesion Molecules; D024141:Collagen Type IV; D016023:Integrins; D007797:Laminin; D008562:Membrane Glycoproteins; C112846:Nid2 protein, mouse; C089141:laminin gamma 1; C029967:nidogen