The calcium-activated neutral protease calpain I is present in normal foetal skin and is decreased in neonatal harlequin ichthyosis.
Calcium concentration is a critical factor for epidermal differentiation and is implicated in the expression and post-translational modification of numerous proteins in suprabasal cells of the epidermis. Calpains (calcium-activated neutral proteases) are believed to participate in signal transduction via highly regulated cytoplasmic protease activity. Here we investigate the expression of calpain I in normal human skin development and in neonatal harlequin ichthyosis (HI), a disorder of altered epidermal differentiation, especially the transition from the granular to the fully differentiated cornified layer. Calpain I was detected in developing foetal epidermis at 54 days estimated gestational age in the basal layer and the periderm of the developing foetal epidermis. By 125 days, calpain I was also detected in the granular layer. This pattern was maintained in newborn skin, but expression was significantly weaker in HI biopsies (n = 7). Reduced expression of calpain was specific to HI and was not observed in other skin diseases. Calpain was also normally expressed in the outer root sheath of hair follicles, in sebaceous glands and in sweat ducts and glands. Immunoblots of epidermal and keratinocyte extracts showed that the 78-kDa and 76-kDa active forms were generated via limited proteolysis of the 80-kDa inactive subunit; however, all forms were diminished in HI, consistent with findings in tissue sections. Our results show that calpain is present throughout the epidermis and is expressed from the early stages of development. These findings implicate calcium-mediated signalling events in the alteration of differentiation that occurs in HI.
Michel
M
M
Department of Oral Biology, University of Washington, Seattle, WA 98195-7132, USA. martanas@u.washington.edu
Fleckman
P
P
Smith
L T
LT
Dale
B A
BA
D015415:Biomarkers; D002118:Calcium / Q000502:physiology; D002154:Calpain / Q000378:metabolism*; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000502:physiology; D004817:Epidermis / Q000196:embryology* / Q000201:enzymology*; D005333:Fetus / Q000201:enzymology; D005865:Gestational Age; D006801:Humans; D017490:Ichthyosis, Lamellar / Q000201:enzymology*; D007124:Immunoenzyme Techniques; D007231:Infant, Newborn; D015603:Keratinocytes / Q000201:enzymology; D008297:Male
D015415:Biomarkers; D002154:Calpain; D002118:Calcium