The heparan sulphate deficient Hspg2 exon 3 null mouse displays reduced deposition of TGF-β1 in skin compared to C57BL/6 wild type mice.
This was an observational study where we examined the role of perlecan HS on the deposition of TGF-β1 in C57BL/6 and Hspg2(∆3-/∆3-) perlecan exon 3 null mouse skin. Despite its obvious importance in skin repair and tissue homeostasis no definitive studies have immunolocalised TGF-β1 in skin in WT or Hspg2(∆3-/∆3-) perlecan exon 3 null mice. Vertical parasagittal murine dorsal skin from 3, 6 and 12 week old C57BL/6 and Hspg2(∆3-/∆3-) mice were fixed in neutral buffered formalin, paraffin embedded and 4 μm sections stained with Mayers haematoxylin and eosin (H & E). TGF-β1 was immunolocalised using a rabbit polyclonal antibody, heat retrieval and the Envision NovaRED detection system. Immunolocalisation of TGF-β1 differed markedly in C57BL/6 and Hspg2(∆3-/∆3-) mouse skin, ablation of exon 3 of Hspg2 resulted in a very severe reduction in the deposition of TGF-β1 in skin 3-12 weeks postnatally. The reduced deposition of TGF-β1 observed in the present study would be expected to impact detrimentally on the remodelling and healing capacity of skin in mutant mice compounding on the poor wound-healing properties already reported for perlecan exon 3 null mice due to an inability to signal with FGF-2 and promote angiogenic repair processes. TGF-β1 also has cell mediated effects in tissue homeostasis and matrix stabilisation a reduction in TGF-β1 deposition would therefore be expected to detrimentally impact on skin homeostasis in the perlecan mutant mice.
Raymond Purves Bone and Joint Research Laboratory, Institute of Bone and Joint Research, Kolling Institute Northern Sydney Local Health District, The Royal North Shore Hospital, Level 10, Kolling Institute, Building B6, St. Leonards, NSW, 2065, Australia.
Cindy
C
Shu
Raymond Purves Bone and Joint Research Laboratory, Institute of Bone and Joint Research, Kolling Institute Northern Sydney Local Health District, The Royal North Shore Hospital, Level 10, Kolling Institute, Building B6, St. Leonards, NSW, 2065, Australia.
Susan M
SM
Smith
Raymond Purves Bone and Joint Research Laboratory, Institute of Bone and Joint Research, Kolling Institute Northern Sydney Local Health District, The Royal North Shore Hospital, Level 10, Kolling Institute, Building B6, St. Leonards, NSW, 2065, Australia. james.melrose@sydney.edu.au.|Sydney Medical School, Northern, The University of Sydney, Royal North Shore Hospital, St. Leonards, Australia. james.melrose@sydney.edu.au.|School of Biomedical Engineering, University of New South Wales, Kensington, NSW, 2052, Australia. james.melrose@sydney.edu.au.
James
J
Melrose
D000818:Animals; D005091:Exons; D005838:Genotype; D019812:Heparan Sulfate Proteoglycans / Q000172:deficiency* / Q000235:genetics* / Q000378:metabolism; D006497:Heparan Sulfate / Q000172:deficiency*; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012867:Skin / Q000378:metabolism* / Q000473:pathology; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
D019812:Heparan Sulfate Proteoglycans; D006497:Heparan Sulfate; D053773:Transforming Growth Factor beta1; C071927:perlecan
HS deficiency; Perlecan; Skin; TGF-β