Three-dimensional imaging reveals major changes in skin microvasculature in lipoid proteinosis and lichen sclerosus

Kowaléwski, Cezary; Kozłowska, Anna; Chan, Ien; Górska, M; Woźniak, Katarzyna; Jabłońska, Stefania; McGrath, John A.

doi:10.1016/j.jdermsci.2005.01.012

Cited by 38 publications

(32 citation statements)

References 25 publications

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“…In humans, loss of function mutations in ECM-1 elicit a rare genetic skin disease called lipoid proteinosis [39,40], whose clinicopathological features are phenocopied in patients with lichen sclerosus, an acquired inflammatory disorder of the skin and mucous membranes associated with the development self-reactive ECM-1 antibodies [41]. Interestingly, both skin conditions are characterized by the (i) abnormal development of cutaneous microvessels, and (ii) excessive deposition of basement membrane proteins, leading to thickened mucous and vascular basement membranes [42].…”

Section: Discussionmentioning

confidence: 99%

“…Thus, ECM-1 is an important regulator of basement membrane protein secretion and deposition, and quite possibly, of microenvironment remodeling [42,46]. As such, aberrant ECM-1 production likely dysregulates normal microenvironment conditions operant in balancing pro-and antiangiogenic signals, leading to altered vessel formation and disease development in humans.…”

Section: Discussionmentioning

confidence: 99%

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Transcriptome analysis of endothelial cell gene expression induced by growth on matrigel matrices: identification and characterization of MAGP-2 and lumican as novel regulators of angiogenesis

et al. 2007

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Remodeling of vascular microenvironments during normal and tumor-induced angiogenesis is an important, yet poorly understood mechanism by which endothelial cells (ECs) contribute to the activation or resolution of angiogenesis. We used microarray analyses to monitor changes in the transcriptome of ECs undergoing angiogenesis when cultured onto Matrigel matrices. This strategy identified 308 genes whose expression in ECs was altered at least 3-fold by angiogenesis, of which 63 genes were found to encode for secretory proteins. In vitro assays that modeled key steps in the angiogenic process showed that several identified genes possessed pro- or anti-angiogenic activities (e.g., SMOC-2, secreted modular calcium-binding protein-2; CRELD-2, cysteine-rich with EGF-like domains-1; MAGP-2, microfibril-associated glycoprotein-2; lumican; and ECM-1, extracellular matrix protein-1). In particular, MAGP-2 expression potentiated EC proliferation and p38 MAPK activation stimulated by the pro-angiogenic factors, basic fibroblast growth factor (bFGF), epidermal growth factor (EGF), and vascular endothelial growth factor (VEGF); it also stimulated EC invasion and angiogenic sprouting, and more importantly, promoted the development and infiltration of vessels into Matrigel plugs implanted into genetically normal mice. Conversely, lumican inhibited EC activation of p38 MAPK, as well as their invasion, angiogenic sprouting, and vessel formation in mice. Collectively, our findings provide new insights into how EC stromal remodeling regulates angiogenesis activation and resolution, as well as identify two novel EC-secreted stromal proteins that modulate angiogenesis both in vitro and in vivo.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Transcriptome analysis of endothelial cell gene expression induced by growth on matrigel matrices: identification and characterization of MAGP-2 and lumican as novel regulators of angiogenesis

et al. 2007

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“…12 Almost all the mutations of ECM1 published in LP are supposed to lead to low or absent mRNA or protein expression except very few missense mutations. 13 This study reports an unusual homozygous frame shift mutation in exon 6 in two sisters suffering from LP of a Pakistani family. This mutation in this region has not been reported hitherto.…”

Section: 911mentioning

confidence: 82%

Homozygous frame shift mutation in ECM1 gene in two siblings with lipoid proteinosis

Samdani¹,

Azhar²,

Shahid³

et al. 2011

J Dermatol Case Rep

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Background: The extracellular matrix protein 1 (ECM1) is a glycoprotein, expressed in skin and other tissues. Loss-of-function mutation in ECM1 causes a rare autosomal recessive disorder called lipoid proteinosis. Lipoid proteinosis is presented by varying degrees of skin scars, beaded papules along the eyelid margins, variable signs of hoarseness of voice and respiratory disorders. More than 250 cases of this disorder have been described in the literature, but occurrence of lipoid proteinosis in siblings is very rare. This study was designed to investigate the possible mutation causing lipoid proteinosis in a Pakistani family and to elaborate the scope of possible genetic changes, causing the genodermatosis in Pakistan.Main observations: In this study, two siblings (12 and 9-years sisters) were presented with scaly itchy lesions on whole body, hoarse voice and macroglossia. Their deceased father had similar clinical manifestations but mother and younger brother were unaffected. Blood samples from clinically affected and unaffected family members were collected with informed consent. The coding region of ECM1 gene containing 10 exons were amplified and sequenced.Both the affected siblings were shown to have homozygous frame shift mutation by deletion of the nucleotide T at 507, codon 169, exon 6. This resulted in a frame shift from codon 169 and appearance of a premature stop codon at 177, causing formation of a mutated protein (176 amino acids) instead of normal ECM1 protein (540 amino acids).Conclusion: A case of homozygous 62-bp insertion in ECM1 gene causing lipoid proteinosis has been reported in another Pakistani family. The current study presents a homozygous frame shift mutation supporting an unusual function of ECM1 protein and broadens the spectrum of disease-linked mutations in this rare case of genodermatosis in this region.

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“…This could be due to lack of feedback control in synthesis, processing, secretion or assembly but also reduced turnover. The primary cause are mutations in the ECM1 gene, abolishing ECM1 synthesis or leading to partial loss-of-function [1,2,9,10] and accordingly autoantibodies against ECM1 (lichen sclerosus [1,[22][23][24]) or decrease of ECM1 during aging [25] have been reported to cause similar symptoms. To illuminate further facets of ECM1 function, herein we have focused on the disturbed molecular architecture of the junctional zone in LP, including hemidesmosomal adhesion complexes.…”

Section: Discussionmentioning

confidence: 99%

“…Netherton syndrome). Furthermore it would explain blistering in bullous forms of lichen sclerosus, an acquired skin disease with comparable ultrastructural disturbances where ECM1 function is affected by autoantibodies [22][23][24].…”

Section: Discussionmentioning

confidence: 99%

Junctional basement membrane anomalies of skin and mucosa in lipoid proteinosis (hyalinosis cutis et mucosae)

Mirancea¹,

Haußer²,

Metze³

et al. 2007

Journal of Dermatological Science

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Three-dimensional imaging reveals major changes in skin microvasculature in lipoid proteinosis and lichen sclerosus

Cited by 38 publications

References 25 publications

Transcriptome analysis of endothelial cell gene expression induced by growth on matrigel matrices: identification and characterization of MAGP-2 and lumican as novel regulators of angiogenesis

Transcriptome analysis of endothelial cell gene expression induced by growth on matrigel matrices: identification and characterization of MAGP-2 and lumican as novel regulators of angiogenesis

Homozygous frame shift mutation in ECM1 gene in two siblings with lipoid proteinosis

Junctional basement membrane anomalies of skin and mucosa in lipoid proteinosis (hyalinosis cutis et mucosae)

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