Functional analysis of stap, a novel gene expressed in hepatic stellate cells and fibrotic liver tissue and its significance in clinicopathophysiology

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STAP consists of a new class of hexacoordinate globin superfamily, which was recently discovered by a proteomics approach for the rat hepatic stellate cells. Unlike hemoglobin, myoglobin and neuroglobin, cytoglobin/STAP is. ubiquitously expressed in several organs although its deteiled localization is unclarified. Immunohistochemistry and immunoelectronmicroscopy revealed that cytoglobin/STAP is uniquely localized in fibroblast-like cells in splanchnic organs, namely vitamin A-storing cell lineage, but neither in epithelial cells, endothelial cells, muscle cells, blood cells, macrophages, nor dermal fibroblasts. Expression of cytoglobin/STAP was upregulated in fibrotic lesions of pancreas and kidney in which activated fibroblast-like cells or myofibroblasts increased in number. In cultured hepatic stellate cells, cytoglobin/STAP expression was augmented by the stimulation with serum, platelet-derived growth factor-BB and transforming growth factor-beta 1. These results indicate that cytoglobin/STAP is a tissue hemoglobin uniquely localized in splanchnic fibroblastic cell lineage and may play a role in fibrotic organ disorder.