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Mol Med. 1997 October; 3(10): 654–662.
PMCID: PMC2230233

Altered procollagen mRNA expression during the progression of avian scleroderma.

Abstract

BACKGROUND: Spontaneous animal models of human autoimmune diseases provide the means to study the very first pathogenetic events, which is not possible in their human counterparts. This is particularly true for connective tissue diseases in which clinical symptoms become manifest only after a long and still obscure course of immunologic, inflammatory, and fibrotic processes. University of California at Davis line 200 chickens (UCD-200) develop a hereditary scleroderma-like disease resembling the entire spectrum of human systemic sclerosis, such as early endothelial cell damage, severe lymphocytic infiltration, and accumulation of collagen in skin and internal organs. MATERIALS AND METHODS: In the present study, we investigated mRNA levels of alpha 1(I), alpha 2(I), alpha 1(II), alpha 1(III), alpha 1(VI), alpha 2(VI), and alpha 3(VI) procollagen and GAPDH using digoxigenin-labeled antisense probes in a nonradioactive ribonuclease protection assay (RPA). We analyzed tissue samples from comb, esophagus, heart, lung, and liver of UCD-200 chickens at different stages of the disease, and healthy UCD-058 chickens. RESULTS: During the early inflammatory stage of the disease, the ratios of procollagen types VI/I and types VI/III increased 7-fold in comb tissue, followed by a 3-fold elevation in type I procollagen transcripts in the late acute stage. In the chronic stage, alpha 1(III) procollagen message was increased 2-fold. Additionally, hybridization with the 180 bp alpha 2(I) antisense probe resulted in two bands of 180 bp and 115 bp, respectively, in the RPA. The ratio of these two previously undescribed bands changes in the early stage of the disease both in comb and esophagus. CONCLUSIONS: In an animal model with a spontaneous scleroderma-like disease we found a characteristic, sequential increase in type VI, type I, and type III procollagen transcripts, and we found evidence for the presence and altered ratio of two mRNA variants of alpha 2(I) procollagen, possibly caused by alternative splicing. Comparative analysis of alpha 2(I) procollagen variants in early stages of avian scleroderma and human SSc might provide answers to unresolved questions concerning the molecular basis for generalized fibrosis in scleroderma.

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Selected References

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