The Urokinase Receptor Homolog Haldisin Is a Novel Differentiation Marker of Stratum Granulosum in Squamous Epithelia

Gårdsvoll, Henrik; Kriegbaum, Mette C.; Hertz, Emil Peter Thrane; Alpízar‐Alpízar, Warner; Ploug, Michael

doi:10.1369/0022155413501879

Cited by 19 publications

(30 citation statements)

References 32 publications

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“…Consistent with previous reports, restricted expression in stratum granulosum was found for filaggrin (FLG) and FLG2 (data not shown); Ly6/PLAUR domain-containing protein 5 (LYPD5) (Gardsvoll et al 2013); keratinocyte proline-rich protein (KPRP; Fig. 3O) (Kong et al 2003); premature ovarian failure 1B protein (POF1B; Fig.…”

Section: Proteins Expressed In Stratum Granulosumsupporting

confidence: 91%

Expression of Human Skin-Specific Genes Defined by Transcriptomics and Antibody-Based Profiling

Edqvist

Fagerberg

Hallström

et al. 2014

J Histochem Cytochem.

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To increase our understanding of skin, it is important to define the molecular constituents of the cell types and epidermal layers that signify normal skin. We have combined a genome-wide transcriptomics analysis, using deep sequencing of mRNA from skin biopsies, with immunohistochemistry-based protein profiling to characterize the landscape of gene and protein expression in normal human skin. The transcriptomics and protein expression data of skin were compared to 26 (RNA) and 44 (protein) other normal tissue types. All 20,050 putative protein-coding genes were classified into categories based on patterns of expression. We found that 417 genes showed elevated expression in skin, with 106 genes expressed at least five-fold higher than that in other tissues. The 106 genes categorized as skin enriched encoded for well-known proteins involved in epidermal differentiation and proteins with unknown functions and expression patterns in skin, including the C1orf68 protein, which showed the highest relative enrichment in skin. In conclusion, we have applied a genome-wide analysis to identify the human skin-specific proteome and map the precise localization of the corresponding proteins in different compartments of the skin, to facilitate further functional studies to explore the molecular repertoire of normal skin and to identify biomarkers related to various skin diseases.

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Section: Proteins Expressed In Stratum Granulosumsupporting

confidence: 91%

Expression of Human Skin-Specific Genes Defined by Transcriptomics and Antibody-Based Profiling

Edqvist

Fagerberg

Hallström

et al. 2014

J Histochem Cytochem.

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“…19,23,24 In this system, the GPIHBP1 proteins contained an amino-terminal uPAR tag (detectable with antibody R24) and sequences from the carboxyl terminus of mouse GPIHBP1 (detectable with antibody 11A12). Under nonreducing conditions, 48.8 ± 0.02% ( n = 20 experiments) of the wild-type GPIHBP1 secreted by Drosophila S2 cells was monomeric, as judged by western blots with antibody 11A12 (Figure 1B).…”

Section: Resultsmentioning

confidence: 99%

GPIHBP1 Missense Mutations Often Cause Multimerization of GPIHBP1 and Thereby Prevent Lipoprotein Lipase Binding

Beigneux

Fong

Bensadoun

et al. 2015

Circulation Research

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Rationale GPIHBP1, a GPI-anchored protein of capillary endothelial cells, binds lipoprotein lipase (LPL) in the subendothelial spaces and shuttles it to the capillary lumen. GPIHBP1 missense mutations that interfere with LPL binding cause familial chylomicronemia. Objective We sought to understand mechanisms by which GPIHBP1 mutations prevent LPL binding and lead to chylomicronemia. Methods and Results We expressed mutant forms of GPIHBP1 in Chinese hamster ovary cells, rat and human endothelial cells, and Drosophila S2 cells. In each expression system, mutation of cysteines in GPIHBP1’s Ly6 domain (including mutants identified in chylomicronemia patients) led to the formation of disulfide-linked dimers and multimers. GPIHBP1 dimerization/multimerization was not unique to cysteine mutations; mutations in other amino acid residues, including several associated with chylomicronemia, also led to protein dimerization/multimerization. The loss of GPIHBP1 monomers is quite relevant to the pathogenesis of chylomicronemia because only GPIHBP1 monomers—and not dimers or multimers—are capable of binding LPL. One GPIHBP1 mutant, GPIHBP1-W109S, had distinctive properties. GPIHBP1-W109S lacked the ability to bind LPL but had a reduced propensity for forming dimers or multimers, suggesting that W109 might play a more direct role in binding LPL. In support of that idea, replacing W109 with any of 8 other amino acids abolished LPL binding—and often did so without promoting the formation of dimers and multimers. Conclusions Many amino acid substitutions in GPIHBP1’s Ly6 domain that abolish LPL binding lead to protein dimerization/multimerization. Dimerization/multimerization is relevant to disease pathogenesis, given that only GPIHBP1 monomers are capable of binding LPL.

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“…In the present study, we have examined the expression patterns of C4.4A and Haldisin, two newly discovered squamous differentiation markers (Gårdsvoll et al 2013;Kriegbaum et al 2011), in a collection of skin diseases. Whereas we found no dramatic alterations in their expression signatures in the various blistering lesions covering most of the strata in the squamous epithelium, or in the lesions with dysregulated differentiation, we did observe attenuation in C4.4A expression in the lesion core of invasive squamous cell carcinomas and keratoacanthomas and a recovery of high expression in the deeply invasive fronts.…”

Section: Discussionmentioning

confidence: 99%

“…Recombinant human C4.4A and Haldisin as well as rabbit anti-C4.4A and anti-Haldisin polyclonal antibodies (pAb) were generated and purified as previously described (Gårdsvoll et al 2013;Hansen et al 2004). Rabbit anticytokeratin (CK) 5 pAb (ab24647), mouse anti-CK14 monoclonal antibody (mAb) (ab7800) and rabbit anti-loricrin pAb (ab24722) were purchased from Abcam (Cambridge, UK).…”

Section: Proteins and Antibodiesmentioning

confidence: 99%

Expression of the Ly6/uPAR-Domain Proteins C4.4A and Haldisin in Non-Invasive and Invasive Skin Lesions

Kriegbaum

Clausen

Lærum

et al. 2014

J Histochem Cytochem.

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C4.4A and Haldisin belong to the Ly6/uPAR/α-neurotoxin protein domain family. They exhibit highly regulated expression profiles in normal epidermis, where they are confined to early (C4.4A) and late (Haldisin) squamous differentiation. We have now explored if dysregulated expressions occur in non-invasive and invasive skin lesions. In non-invasive lesions, their expression signatures were largely maintained as defined by that of normal epidermis. The scenario was, however, markedly different in the progression towards invasive squamous cell carcinomas. In its non-invasive stage (carcinoma in situ), a pronounced attenuation of C4.4A expression was observed, but upon transition to malignant invasive squamous cell carcinomas, the invasive fronts regained high expression of C4.4A. A similar progression was observed for the early stages of benign infiltrating keratoacanthomas. Interestingly, this transition was accompanied by a shift in the predominant association of C4.4A expression with CK1/10 in the normal epidermis to CK5/14 in the invasive lesions. In contrast, Haldisin expression maintained its confinement to the most-differentiated cells and was hardly expressed in the invasive lesions. Because this altered expression of C4.4A was seen in the invasive front of benign (keratoacanthomas) and malignant (squamous cell carcinomas) neoplasms, we propose that this transition of expression is primarily related to the invasive process.

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The Urokinase Receptor Homolog Haldisin Is a Novel Differentiation Marker of Stratum Granulosum in Squamous Epithelia

Cited by 19 publications

References 32 publications

Expression of Human Skin-Specific Genes Defined by Transcriptomics and Antibody-Based Profiling

Expression of Human Skin-Specific Genes Defined by Transcriptomics and Antibody-Based Profiling

GPIHBP1 Missense Mutations Often Cause Multimerization of GPIHBP1 and Thereby Prevent Lipoprotein Lipase Binding

Expression of the Ly6/uPAR-Domain Proteins C4.4A and Haldisin in Non-Invasive and Invasive Skin Lesions

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