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Scleroderma lung fibroblasts exhibit elevated and dysregulated type I collagen biosynthesis
X Shi-Wen1, C P Denton, A McWhirter
1Royal Free Hospital, London, UK.
Arthritis and Rheumatism
|July 1, 1997
Summary
Scleroderma lung fibroblasts exhibit increased type I collagen (CI) production and fail to down-regulate CI mRNA in 3-D culture, suggesting a role in lung fibrosis pathogenesis.
Area of Science:
- Connective tissue biology
- Pulmonary medicine
- Fibrotic disease research
Background:
- Scleroderma is associated with lung fibrosis.
- Dermal fibroblasts in scleroderma show aberrant type I collagen (CI) biosynthesis.
- The behavior of lung fibroblasts in scleroderma is less understood.
Purpose of the Study:
- To investigate if scleroderma lung fibroblasts exhibit abnormal type I collagen (CI) synthesis.
- To compare CI biosynthesis in lung fibroblasts from scleroderma patients and healthy controls.
Main Methods:
- Cultured lung fibroblasts from scleroderma patients and controls.
- Measured CI secretion and pro alpha1(I) collagen mRNA levels in monolayer.
- Assessed COL1A2 gene activation and mRNA regulation in 3-D collagen gel matrices.
Main Results:
- Scleroderma lung fibroblasts secreted significantly more CI than controls.
- Pro alpha1(I) collagen mRNA levels were higher in scleroderma fibroblasts.
- Scleroderma fibroblasts showed transcriptional activation of CI genes and failed to down-regulate mRNA in 3-D culture.
Conclusions:
- Scleroderma lung fibroblasts demonstrate elevated CI biosynthesis.
- Impaired mRNA down-regulation of CI in scleroderma lung fibroblasts was observed.
- These findings are relevant to the pathogenesis of scleroderma-associated lung fibrosis.