Uroporphyrin I Stimulation of Collagen Biosynthesis in Human Skin Fibroblasts

Abstract

A B S T R A C T Porphyria cutanea tarda and erythropoietic porphyria are disorders of heme synthesis that originate in the liver and bone marrow, respectively. Each is characterized by increased accumulation of uroporphyrin, I, by cutaneous photosensitivity, and in some patients by indurated plaques and scarring that resemble scleroderma. These scleroderma-like lesions occur in light-exposed and light-protected body areas. In these studies we evaluated the role of uroporphyrin I and of light in evoking the scleroderma-like cutaneous changes. Normal human skin fibroblasts were exposed to uroporphyrin I and to 400 nm radiation and the effect of these agents on collagen accumulation by the cells was determined. Radioactive tracer studies showed that uroporphyrin I caused a specific increase in the accumulation of newly synthesized collagen by fibroblast monolayer cultures, as verified by [3H]hydroxyproline and collagenase digestion assays. Collagen accumulation was stimulated 1.5-to 2.7-fold by uroporphyrin I, whereas noncollagenous protein accumulation was unchanged. The increased collagen accumulation was time and uroporphyrin I-concentration-dependent, and occurred both in the presence or absence of ultraviolet light exposure. Further studies demonstrated that the increased accumulation was not the result of decreased rates of collagen degradation nor was it due to changes in cell population growth parameters (generation times and saturation densities).

Porfiria cutânea tardia

“…41 Fibroblast proliferation and fibrosisEnhanced biosynthesis of collagen occurs after incubation of fibroblasts with URO, irrespective of light radiation. 42 C' activation causes generation of anaphylotoxin (C5a), 33 releasing histamine form mast cells, which stimulate collagen production. 43 Fibrosis may also be secondary to vascular injury.…”

The photodynamic and non-photodynamic actions of porphyrins

“…In 1982, it was reported that URO stimulates collagen biosynthesis in human skin fibroblasts (32), and that PROTO activates guanylate cyclase in the dark (33). Decreased cytochrome c oxidase activity and increased · OH lactate production and glucose utilization were induced by porphyrin derivatives in cell cultures (34).…”

Increased Mast Cell Numbers in the Sclerotic Skin of Porphyria cutanea tarda

“…Uroporphyrin I was also found to cause increased collagen synthesis by fibro blasts in vitro, with or without the exposure to ultraviolet radiation [8], and the sclerodermoid lesions in PCT are reported to be not always confirmed to light-exposed areas. However, in our PCT patients, the sclerosis was observed only in chronically light-exposed skin.…”