Srcasm overexpression in psoriasis-insights into pathogenesis.
Academic Article
Overview
abstract
BACKGROUND: Psoriasis is a prevalent, chronic cutaneous disorder associated with a T-cell lymphocytic infiltrate and altered keratinocyte growth. Some of the molecular features of enhanced keratinocyte growth include increased growth factor receptor activation leading to enhanced cellular tyrosine kinase activity. Receptor tyrosine kinases, including the epidermal growth factor (EGF) receptor, are important regulators of keratinocyte growth, and increased activity of this receptor has been detected in psoriasis. A recently discovered, novel regulator of Src tyrosine kinases, termed Src-activating and signaling molecule (Srcasm), has been shown to modulate EGF signaling and promote differentiation in human keratinocytes. Given the properties of Srcasm, it would be of interest to characterize its expression in psoriasis. In this study, the levels of Srcasm mRNA and protein are characterized, and the relationship of these experimental observations to the psoriasis pathogenesis is discussed. METHODS: The levels of Srcasm mRNA were determined by quantitative reverse transcriptase polymerase chain reaction (RT-PCR) on RNA isolated from unremarkable and lesional patient tissue. These data were supplemented by performing radioactive in situ hybridization on formalin-fixed biopsy specimens of psoriatic lesions and unremarkable epidermis. Expression of Srcasm protein was evaluated by protein immunohistochemistry and Western blotting of protein lysates derived from patient samples. RESULTS: All experimental modalities show that levels of Srcasm mRNA and protein were elevated in psoriatic lesions compared to unremarkable epidermis. CONCLUSIONS: Increased levels of Srcasm mRNA and protein are seen in psoriasis. Given what is known regarding Srcasm function, increased levels of this molecule in keratinocytes may represent a cell compensatory mechanism that is primed to re-establish a physiologic differentiation program.
