Negligible Contribution of Bone Marrow-Derived Cells to Collagen Production During Hepatic Fibrogenesis in Mice

Identification of a novel alpha‐fetoprotein‐expressing cell population induced by the Jagged1/Notch2 signal in murine fibrotic liver

“…At 8 weeks of age, Jagged1 cKO mice and control Mx‐Cre ‐negative Jagged1 lox/lox littermates were given a total of four injections of 250 μg of poly(I):poly(C) (Sigma‐Aldrich, St. Louis, MO) every 3 days 16. Approximately 8 weeks after the poly(I):poly(C) injections, the mice started to receive subcutaneous injections of 1 mL/kg body weight of CCl 4 (Wako Pure Chemical Industries, Ltd., Tokyo, Japan) mixed in olive oil every 3 days for a total of 28‐30 times 17. Acute liver injury was induced in wild‐type mice by an intraperitoneal injection of CCl 4 or thioacetamide.…”

“…In some experiments, mice were fed a 3,5‐diethoxycarbonyl‐1,4‐dihydrocollidine (DDC) diet (Oriental Yeast, Tokyo, Japan) or a methionine choline‐deficient ethionine‐supplemented diet (MP Biomedicals, Santa Ana, CA). Bile duct ligation and 70% partial hepatectomy were performed as described 17, 18…”

“…Histological and immunohistological studies were performed as described 17, 19, 20. Briefly, formalin‐fixed and paraffin‐embedded sections were subjected to hematoxylin/eosin or sirius red‐fast green FCF staining using standard protocols.…”

“…HSC were prepared using the pronase/collagenase perfusion method17 and seeded on a type I collagen‐coated 24‐well plate or chamber slides (AGC Techno Glass, Shizuoka, Japan). They were cultured using Dulbecco's modified Eagle medium supplemented with 10% fetal bovine serum and nonessential amino acids.…”

Cellular and Molecular Mechanisms of Chronic Inflammation-Associated Organ Fibrosis

“…However, it remains unclear whether the cognate chemokines regulate organ fibrosis through the recruitment of fibrocytes to the inflamed tissues, by influencing the activation or differentiation of fibroblasts, or through the recruitment of inflammatory cells such as macrophages and neutrophils that subsequently influence the tissue microenvironment. While many studies have confirmed the presence of fibrocytes in fibrotic disease, accumulating experimental evidence suggests that the contribution of bone marrowderived cells to the Col I producing fibroblast/myofibroblast pool is limited (Higashiyama et al, 2009(Higashiyama et al, , 2011.…”