TY - JOUR
T1 - Impaired wound healing in mice lacking the basement membrane protein nidogen 1
AU - Baranowsky, Anke
AU - Mokkapati, Sharada
AU - Bechtel, Manuela
AU - Krügel, Jenny
AU - Miosge, Nicolai
AU - Wickenhauser, Claudia
AU - Smyth, Neil
AU - Nischt, Roswitha
N1 - Funding Information:
We wish to gratefully acknowledge the excellent technical assistance by Marion Reibetanz and Jan Zamek (Department of Dermatology, University of Cologne) and Silke Kummer (Institute for Pathology, University of Cologne). This work was supported by grants from the Deutsche Forschungsgemeinschaft through the SFB 589 and 829 at the University of Cologne (RN) and the grant NI-304/11-1 (RN).
PY - 2010/1
Y1 - 2010/1
N2 - 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 α-smooth muscle actin staining in the dermis of nidogen 1 deficient wounds at this time point. Further, laminin deposition and distribution of the β1 and β4 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.
AB - 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 α-smooth muscle actin staining in the dermis of nidogen 1 deficient wounds at this time point. Further, laminin deposition and distribution of the β1 and β4 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.
KW - Basement membrane
KW - Epidermal differentiation
KW - Nidogen 1 deficient mice
KW - Nidogen 2
KW - Skin
KW - Wound repair
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U2 - 10.1016/j.matbio.2009.09.004
DO - 10.1016/j.matbio.2009.09.004
M3 - Article
C2 - 19766719
AN - SCOPUS:73449146600
SN - 0945-053X
VL - 29
SP - 15
EP - 21
JO - Matrix Biology
JF - Matrix Biology
IS - 1
ER -