The heparan sulphate deficient Hspg2 exon 3 null mouse displays reduced deposition of TGF-β1 in skin compared to C57BL/6 wild type mice

• Published in: Journal of molecular histology 2016-06, Vol.47 (3), p.365-374
• Main Authors: Shu, Cindy, Smith, Susan M., Melrose, James
• Format: Article
• Language: English
• Subjects: Animals; Biomedical and Life Sciences; Biomedicine; Cell Biology; Developmental Biology; Exons; Genotype; Heparan Sulfate Proteoglycans - deficiency; Heparan Sulfate Proteoglycans - genetics; Heparan Sulfate Proteoglycans - metabolism; Heparitin Sulfate - deficiency; Immunohistochemistry; Life Sciences; Mice; Mice, Inbred C57BL; Mice, Knockout; Original Paper; Skin - metabolism; Skin - pathology; Transforming Growth Factor beta1 - metabolism
• ISSN: 1567-2379; 1567-2387
• DOI: 10.1007/s10735-016-9677-0

This was an observational study where we examined the role of perlecan HS on the deposition of TGF-β1 in C57BL/6 and Hspg 2 ∆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 Hspg 2 ∆3−/∆3− perlecan exon 3 null mice. Vertical parasagittal murine dorsal skin from 3, 6 and 12 week old C57BL/6 and Hspg 2 ∆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 Hspg 2 ∆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.