Hsp47 a novel collagen binding serpin chaperone, autoantigen and therapeutic target

Hsp47 was originally discovered as a cell surface collagen binding protein, colligin, and was later shown to be an endoplasmic reticulum ( ER) resident protein with collagen binding properties in chick fibroblasts. Hsp47 has been termed J6, gp46, CB48 and CBP2 in various other organisms and has been mapped to human chromosome 11q13.5 a known hot spot in a number of human cancers. Hsp47 has been shown to be constitutively expressed with collagens; it is heat inducible and binds to both helical and non-helical forms of collagens. Hsp47 binds closely to procollagen in the ER, but dissociates from it in the cis-Golgi to allow fibril formation. Hsp47 is over-expressed in many fibrotic diseases including: glomerulosclerosis, pulmonary fibrosis, liver cirrhosis, cicatricial pemphigoid, epidermolysis bullosa acquista and keloids. Hsp47 is associated with fibrosis following myocardial infarction and has been localized in artherosclerotic arteries. Among a number of rheumatoid conditions, Hsp47 manifests properties of an autoantigen and in some cancers appears to be a biomarker. The unique properties of Hsp47 in modulating collagen production and its location to the cell membrane in many forms of cancer have designated Hsp47 as a potential biomarker and/or therapeutic target for a number of conditions and diseases.