Rare Diseases Symptoms Automatic Extraction

Partial loss of epithelial phenotype in kindlin-1-deficient keratinocytes.

[kindler syndrome]

Kindlin-1 is an adaptor protein that is expressed by most epithelial cells and has been implicated in integrin bidirectional signaling. Mutations in the gene encoding kindlin-1 are associated with Kindler syndrome, a recessively inherited disorder that is characterized by fragile skin. Functionally, a loss of kindlin-1 impairs the adhesion of basal keratinocytes to the extracellular matrix both in vivo and in vitro. In this study, we show that the phenotype of mutant keratinocytes deficient in kindlin-1 is characterized by the modification of the cortical actin network and increased plasticity of the plasma membrane. At the molecular level, expression of several proteins associated with an epithelial phenotype, such as α6β4 integrin, collagen XVII, E-cadherin, and desmoglein-3, is strongly reduced, whereas, surprisingly, laminin 332 is synthesized in larger amounts than in control keratinocytes. In contrast, mesenchymal markers such as vimentin and fibronectin are increased in keratinocytes lacking kindlin-1. The switch in cell plasticity and protein expression was confirmed by siRNA-mediated down-regulation of kindlin-1 in HaCaT epithelial cells. Furthermore, there was up-regulation of matrix metalloproteinases and pro-inflammatory cytokines in kindlin-1-deficient keratinocytes. These results provide new insights into the pathogenic mechanisms that take place in Kindler syndrome. Moreover, the constellation of molecular defects associated with the loss of kindlin-1 may explain the higher incidence of skin cancer observed in patients affected with this disorder.

Diseases presenting "basal keratinocytes" symptom

  • dystrophic epidermolysis bullosa
  • epidermolysis bullosa simplex
  • harlequin ichthyosis
  • junctional epidermolysis bullosa
  • kindler syndrome
  • lamellar ichthyosis
  • severe combined immunodeficiency

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