Kazuko Osada

Decreased integrin α2, but normal response to TGF-β in scleroderma fibroblasts

The distribution and amount of integrin α2 were studied in cultured fibroblasts from normal subjects and scleroderma patients by immunofluorescence and immunoblotting using a monoclonal antibody against the human integrin α2 subunit. Integrin α2 was concentrated at the perinuclear regions in a dot-like pattern in normal fibroblasts on the glass coverslips until the 14th day after planting, and the staining pattern of integrin α2 was gradually changed to a dispersed dot-like pattern by the 19th day as examined by immunofluorescence microscopy by using the anti-integrin α2 antibody. No difference was observed in the distribution patterns between normal and scleroderma fibroblasts. By immunoblotting study, the amount of integrin α2 in scleroderma fibroblasts (n = 10) was less than that of normal fibroblasts (n = 10) (P < 0.01) in both cytosol and cytoskeleton-associated fractions. Furthermore, transforming growth factor β (TGF-β) increased the amount of integrin α2 in both normal fibroblasts and scleroderma cells by 33%. The total amount of integrin α2 in TGF-β-stimulated scleroderma fibroblasts was less than that in TGF-β-stimulated normal fibroblasts. These findings suggest that the amount of integrin α2, a collagen receptor, is reduced in scleroderma fibroblasts, but the integrin α2 production by TGF-β stimulation is not impaired in scleroderma fibroblasts.

Etretinate administration reduces serum propeptide of type I procollagen level in patients with psoriasis

The serum carboxyterminal propeptide of type I procollagen (PICP) level in 26 patients with psoriasis was significantly lower than in control subjects (124 + 47 and 224 + 78 ng/ml, respectively: P < 0.001). The patients were divided into two groups, those treated with etretinate and untreated patients. PICP levels in the treated group were significantly lower than those in the untreated group (P < 0.001), but there was no difference between the control and untreated groups. In addition, there was a negative correlation between PICP levels and the serum etretinate concentration in treated patients (r=−0.622, P < 0.05).

Decreased bradykinin binding sites in fibroblasts from progressive systemic scleroderma

The numbers of bradykinin receptors (BK-R) in cultured dermal fibroblasts from patients with progressive systemic sclerosis (PSS) and from healthy controls were measured using a receptor binding assay. The numbers of BK-R were significantly fewer in PSS fibroblasts than in control fibroblasts (P<0.02). However, no differences in affinity were observed in BK-R between PSS and control fibroblasts. The BK-R mRNA levels were determined in PSS and control fibroblasts by Northern blot hybridization using BK-R cDNA, but no significant differences were found. These findings suggest that the decrease in BK-R in PSS fibroblasts might occur during a posttranslational step.