Biology of anchoring fibrils: lessons from dystrophic epidermolysis bullosa

Bruckner‐Tuderman, Leena; Höpfner, Bianca; Hammami-Hauasli, Nadja

doi:10.1016/s0945-053x(98)00007-9

Cited by 101 publications

(68 citation statements)

References 59 publications

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“…In normal human skin, the C-propeptide is completely removed and is not found at the dermal-epidermal junction. However, in dystrophic epidermolysis bullosa (DEB), a genetic disease caused by mutations of collagen VII (30,31), procollagen can be retained in the skin of the patient, implying that deficient C-propeptide processing is associated with functional abnormalities of the anchoring fibrils (32). The importance of the NC-2 domain for antiparallel dimer formation was recently demonstrated by Chen et al (33).…”

mentioning

confidence: 99%

Proteinases of the Bone Morphogenetic Protein-1 Family Convert Procollagen VII to Mature Anchoring Fibril Collagen

Rattenholl¹,

Pappano²,

Koch³

et al. 2002

Journal of Biological Chemistry

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109

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Collagen VII is the major structural component of the anchoring fibrils at the dermal-epidermal junction in the skin. It is secreted by keratinocytes as a precursor, procollagen VII, and processed into mature collagen during polymerization of the anchoring fibrils. We show that bone morphogenetic protein-1 (BMP-1), which exhibits procollagen C-proteinase activity, cleaves the Cterminal propeptide from human procollagen VII. The cleavage occurs at the BMP-1 consensus cleavage site SYAA2DTAG within the NC-2 domain. Mammalian tolloid-like (mTLL)-1 and -2, two other proteases of the astacin enzyme family, were able to process procollagen VII at the same site in vitro. Immunohistochemical and genetic evidence supported the involvement of these enzymes in cleaving type VII procollagen in vivo. Both BMP-1 and mTLL-1 are expressed in the skin and in cultured cutaneous cells. A naturally occurring deletion in the human COL7A1 gene, 8523del14, which is associated with dystrophic epidermolysis bullosa and eliminates the BMP-1 consensus sequence, abolished processing of procollagen VII, and in mutant skin procollagen VII accumulated at the dermal-epidermal junction. On the other hand, deficiency of BMP-1 in the skin of knockout mouse embryos did not prevent processing of procollagen VII to mature collagen, suggesting that mTLL-1 and/or mTLL-2 can substitute for BMP-1 in the processing of procollagen VII in situ.

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mentioning

confidence: 99%

Proteinases of the Bone Morphogenetic Protein-1 Family Convert Procollagen VII to Mature Anchoring Fibril Collagen

Rattenholl¹,

Pappano²,

Koch³

et al. 2002

Journal of Biological Chemistry

Self Cite

109

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“…Although Chen and others have proposed using a collagen VII 'minigene' with an internal 2 kb deletion for corrective gene transfer of collagen VII in DEB keratinocytes, 37 several reports on the genetic defects in DEB have clearly demonstrated that deletions in the COL7A1 gene are associated with a pathologic phenotype. 3,4,15,38 Therefore, despite technical problems with the delivery of large constructs, therapeutic approaches using a deleted gene are not likely to result in the desired normal phenotype. For these reasons we chose to isolate and use a genomic clone containing the complete COL7A1 gene rather than cDNA sequences in our study.…”

Section: Discussionmentioning

confidence: 99%

“…have only 50% of collagen VII in the skin but are phenotypically and functionally completely normal. 4,15 This observation suggests that the goal of high efficiency gene transfer that restores normal gene expression to all cells is not necessary for a corrective gene therapy of severe recessive DEB. Instead, a 50% level of normal collagen VII expression in the keratinocyte grafts should produce good therapeutic effects.…”

Section: Discussionmentioning

confidence: 99%

“…In milder DEB subtypes, collagen VII protein is expressed but the anchoring fibrils are morphologically altered. 3,4,10 In the most severe DEB form, both collagen VII and anchoring fibrils are absent from the skin, [11][12][13][14] and the clinical course of the disease is dramatic with extensive blistering and scarring which leads to fusion of the digits of the hands and feet, so called mitten hands. Therefore, this recessively inherited severe subtype is also called mutilating DEB.…”

Section: Introductionmentioning

confidence: 99%

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Tissue-specific expression and long-term deposition of human collagen VII in the skin of transgenic mice: implications for gene therapy

et al. 2000

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We report the isolation of a cosmid clone containing the entire human COL7A1 gene in one piece. The ability of the genomic sequences within this clone to direct tissue-specific expression of human collagen VII in transgenic mice was tested. The data show that the gene construct is capable of directing expression of collagen VII in the skin of fetal and neonatal transgenic mice. Expression of COL7A1 in these mice was widespread, in a pattern consistent with that found in human tissues and was in parallel with that of the endogenous mouse gene. Immunostaining, using humanspecific antibodies, showed that human collagen VII protein

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“…Collagen VII is synthesized in keratinocytes and fibroblasts as a procollagen molecule pro-a1 (VII) polypeptide, and is a major structural component of the anchoring fibrils (Chen et al, 1997). Collagen VII may enable the adhesion of the epidermis and the dermis (Bruckner-Tuderman et al, 1999). More than 60 mutations in COL7A1 have been described in DEB-Pr (Fortuna et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Case Report Novel and recurrent COL7A1 mutations in Chinese patients with dystrophic epidermolysis bullosa pruriginosa

Zhu

Zhou

et al. 2014

Genet. Mol. Res.

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ABSTRACT. Dystrophic epidermolysis bullosa pruriginosa (DEBPr) is a rare subtype of dystrophic epidermolysis bullosa (DEB). This disease is characterized by severe itching, lichenoid nodules or prurigolike lesions, and linear scarring with a predilection for the extensor limbs. Pathogenic mutations in the type VII collagen alpha 1 (COL7A1) gene have been identified. We analyzed mutations in the COL7A1 gene in a Chinese family including 5 affected individuals with typical DEBPr and in a patient previously reported with sporadic DEB-Pr. The entire coding region and exon-intron boundaries of COL7A1 were detected by polymerase chain reaction and direct sequencing. We identified one novel heterozygote mutation (c.6842G>T, p.G2281V) and a second mutation (c.5443G>A, p.G1815R) reported previously in patients with DEB. Our findings contribute to the COL7A1 mutation database and further reveal the genetic and phenotypic heterogeneity of DEB-Pr.

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Biology of anchoring fibrils: lessons from dystrophic epidermolysis bullosa

Cited by 101 publications

References 59 publications

Proteinases of the Bone Morphogenetic Protein-1 Family Convert Procollagen VII to Mature Anchoring Fibril Collagen

Proteinases of the Bone Morphogenetic Protein-1 Family Convert Procollagen VII to Mature Anchoring Fibril Collagen

Tissue-specific expression and long-term deposition of human collagen VII in the skin of transgenic mice: implications for gene therapy

Case Report Novel and recurrent COL7A1 mutations in Chinese patients with dystrophic epidermolysis bullosa pruriginosa

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