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1.
Clin Exp Dermatol ; 41(6): 667-70, 2016 Aug.
Article in English | MEDLINE | ID: mdl-27378586

ABSTRACT

Elastosis perforans serpiginosa (EPS) is a rare skin disorder characterized by transepidermal elimination of abnormal elastic fibres. We present a new case of D-penicillamine (DPA)-induced EPS, and describe the clinical, dermoscopic, histopathological and direct immunofluorescence (DIF) findings. A 33-year-old woman receiving treatment with DPA presented with annular skin lesions. Digital dermoscopy of the lesions showed a central area of pink and yellowish discolouration with keratotic papules in the periphery, surrounded by a white halo, disposed in a way that resembled the islands of an archipelago. Other lesions showed a white to yellow central colouration and 'chrysalides' surrounding the keratotic plugs. Linear and granular deposits of IgG attached to the abnormal elastic fibres were seen with DIF. Dermoscopy can be helpful in the diagnosis of EPS. Moreover, DIF findings in skin biopsies of this case support the immune-mediated pathogenesis of EPS.


Subject(s)
Dermoscopy/methods , Fluorescent Antibody Technique, Direct/methods , Penicillamine/adverse effects , Skin Diseases/chemically induced , Adult , Chelating Agents/adverse effects , Chelating Agents/therapeutic use , Elastic Tissue/pathology , Female , Hepatolenticular Degeneration/complications , Hepatolenticular Degeneration/drug therapy , Hepatolenticular Degeneration/pathology , Humans , Penicillamine/administration & dosage , Penicillamine/therapeutic use , Rare Diseases , Skin/pathology , Skin Diseases/pathology
2.
Cell Death Dis ; 6: e1644, 2015 Feb 12.
Article in English | MEDLINE | ID: mdl-25675304

ABSTRACT

Albuminuria promotes tubular injury and cell death, and is associated with faster progression of chronic kidney disease (CKD) to end-stage renal disease. However, the molecular mechanisms regulating tubular cell death in response to albuminuria are not fully understood. Brain abundant signal protein 1 (BASP1) was recently shown to mediate glucose-induced apoptosis in tubular cells. We have studied the role of BASP1 in albumin-induced tubular cell death. BASP1 expression was studied in experimental puromycin aminonucleoside-induced nephrotic syndrome in rats and in human nephrotic syndrome. The role of BASP1 in albumin-induced apoptosis was studied in cultured human HK2 proximal tubular epithelial cells. Puromycin aminonucleoside induced proteinuria and increased total kidney BASP1 mRNA and protein expression. Immunohistochemistry localized the increased BASP1 to tubular cells. BASP1 expression colocalized with deoxynucleotidyl-transferase-mediated dUTP nick-end labeling staining for apoptotic cells. Increased tubular BASP1 expression was observed in human proteinuric nephropathy by immunohistochemistry, providing evidence for potential clinical relevance. In cultured tubular cells, albumin induced apoptosis and increased BASP1 mRNA and protein expression at 6-48 h. Confocal microscopy localized the increased BASP1 expression in albumin-treated cells mainly to the perinuclear area. A peripheral location near the cell membrane was more conspicuous in albumin-treated apoptotic cells, where it colocalized with actin. Inhibition of BASP1 expression by a BASP1 siRNA protected from albumin-induced apoptosis. In conclusion, albumin-induced apoptosis in tubular cells is BASP1-dependent. This information may be used to design novel therapeutic approaches to slow CKD progression based on protection of tubular cells from the adverse consequences of albuminuria.


Subject(s)
Albumins/pharmacology , Calmodulin-Binding Proteins/metabolism , Cytoskeletal Proteins/metabolism , Membrane Proteins/metabolism , Nerve Tissue Proteins/metabolism , Repressor Proteins/metabolism , Animals , Apoptosis/drug effects , Apoptosis/genetics , Blotting, Western , Calmodulin-Binding Proteins/genetics , Cell Line , Cytoskeletal Proteins/genetics , Female , Humans , Immunohistochemistry , Kidney Tubules, Proximal/cytology , Kidney Tubules, Proximal/metabolism , Male , Membrane Proteins/genetics , Microscopy, Confocal , Nerve Tissue Proteins/genetics , RNA, Small Interfering/genetics , Rats , Repressor Proteins/genetics
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