A novel deactivation factor of fibrogenic hepatic stellate cells induces regression of liver fibrosis in mice

It has been reported that hepatic stellate cells (HSCs) differentiate from mesodermal-derived submesothelial cells during embryonic development, and that these cells express a common surface marker p75 neurotrophin receptor (p75NTR). We sorted p75NTR-expressing cells in embryonic liver at each developmental stage, and transcription profiles were analyzed using the DNA microarray. Liver tissues obtained from E11.5, E13.5, E14.5, and E17.5 fetuses or newborn mice (P1) were excised under a microscope and dissociated in 0.05% collagenase solution. The CD45(−)Ter119(−)p75NTR(+) cell fraction was obtained by FACS. Total RNA was prepared from isolated these cells and transcription profiles were analyzed using the DNA microarray. Hierarchical clustering of normalized signal intensities was performed using Euclidean distances and centroid linkage. Raw intensity values were normalized using the 75th percentile and transformed to log2 scale.