Collagen, overproduction

Another important 2-OG dependent oxygenase in mammals is prolyl-4 hydroxylase, which catalyzes the hydroxylation of the proline residue in collagen (Scheme 5). This reaction is essential for the structure of the collagen triple helices (9,34 6). An overproduction of collagen is related to fibrotic diseases such as rheumatic arthritis. Thus collagen prolyl-4 hydroxylase is a target for therapeutics (34,36). 

Both single- and double-stranded DNA are antigenic antibodies to DNA are normally found in the circulation, but in some individuals overproduction of DNA antibodies causes disease. In particular, patients with systemic lupus erythematosus (SLE) show abnormal levels of antibodies to double-stranded DNA. Antibodies to single-stranded DNA also bind to bases, nucleosides, nucleotides, oligonucleotides, and the ribose-phosphate backbone of RNA. Antibodies to double-stranded DNA also bind to base pairs, chromatin, nucleosomes, type IV collagen, and the deoxyribose-phosphate backbone of DNA. 

The cause of scleroderma is unknown. It belongs to a larger group of diseases sometimes classed as collagen diseases. In scleroderma, the changes in the skin and internal organs seem to be due to the overproduction of collagen—connective tissue. 

The main feature of SSc is overproduction and accumulation of collagen and some other extracellular matrix proteins in the skin and other organs. The fibrosis is usually preceded by vascular injury involving small arteries, arterioles and capillaries in the skin, lungs, gastrointestinal tract, kidneys and heart. 

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