Neutralization of CXCL10 accelerates liver regeneration in carbon tetrachloride-induced acute liver injury Export

@article{Yoneyama:2007p723, abstract = {Remodeling of hepatic tissue structure following injury requires the coordinated action of hepatocytes, hepatic stellate cells (HSCs), and endothelial cells. However, their in vivo properties are not fully understood. We report here that the chemokine CXCL10 regulates hepatic tissue remodeling in a carbon tetrachloride (CCl(4))-induced acute liver injury in mice. The production of CXCL10 was enhanced by hepatocytes after CCl(4) exposure. Neutralization of CXCL10 protected mice from acute liver dysfunction and diminished hepatocellular loss. The hepatoprotective effect was associated with increased numbers of 5'-bromo-2' deoxyuridine (BrdU)+ hepatocytes from day 1 and with accumulation of HSCs and endothelial cells within the injured zones from day 3. In vitro, recombinant CXCL10 directly inhibited the proliferation of hepatocytic cells, establishing a novel role of CXCL10 in modulating hepatocyte proliferation, in addition to a previously reported angiostatic role. In summary, neutralization of CXCL10 initially stimulates hepatocyte proliferation and, subsequently, HSC migration and angiogenesis to facilitate remodeling of hepatic cords. Thus, CXCL10 can be a novel therapeutic target for acute hepatocellular damage by regulating liver tissue remodeling.}, author = {Yoneyama, Hiroyuki and Kai, Yoshiro and Koyama, Jun and Suzuki, Kenji and Kawachi, Hiroshi and Narumi, Shosaku and Ichida, Takafumi}, citeulike-article-id = {3046187}, citeulike-linkout-0 = {http://www.springerlink.com/content/627vr622t4401082/}, citeulike-linkout-1 = {http://dx.doi.org/10.1007/s00795-007-0371-x}, doi = {10.1007/s00795-007-0371-x}, journal = {Med Mol Morphol}, keywords = {acute, alanine, animals, c57bl, carbon, cell, chemokine, cxcl10, failure, female, file-import-08-07-27, hepatocytes, inbred, liver, messenger, mice, neutralization, proliferation, proteins, recombinant, regeneration, rna, tests, tetrachloride, transaminase, up-regulation}, local-url = {file://localhost/Users/ken/Documents/Papers/2007/Yoneyama/Med\%20Mol\%20Morphol\%202007\%20Yoneyama-1.pdf}, month = {Dec}, number = {4}, pages = {191--7}, posted-at = {2008-07-27 14:46:02}, priority = {2}, title = {Neutralization of CXCL10 accelerates liver regeneration in carbon tetrachloride-induced acute liver injury}, url = {http://dx.doi.org/10.1007/s00795-007-0371-x}, volume = {40}, year = {2007} }

TY - JOUR ID - Yoneyama:2007p723 L3 - citeulike-article-id:3046187 N2 - Remodeling of hepatic tissue structure following injury requires the coordinated action of hepatocytes, hepatic stellate cells (HSCs), and endothelial cells. However, their in vivo properties are not fully understood. We report here that the chemokine CXCL10 regulates hepatic tissue remodeling in a carbon tetrachloride (CCl(4))-induced acute liver injury in mice. The production of CXCL10 was enhanced by hepatocytes after CCl(4) exposure. Neutralization of CXCL10 protected mice from acute liver dysfunction and diminished hepatocellular loss. The hepatoprotective effect was associated with increased numbers of 5'-bromo-2' deoxyuridine (BrdU)+ hepatocytes from day 1 and with accumulation of HSCs and endothelial cells within the injured zones from day 3. In vitro, recombinant CXCL10 directly inhibited the proliferation of hepatocytic cells, establishing a novel role of CXCL10 in modulating hepatocyte proliferation, in addition to a previously reported angiostatic role. In summary, neutralization of CXCL10 initially stimulates hepatocyte proliferation and, subsequently, HSC migration and angiogenesis to facilitate remodeling of hepatic cords. Thus, CXCL10 can be a novel therapeutic target for acute hepatocellular damage by regulating liver tissue remodeling. IS - 4 JF - Med Mol Morphol EP - 7 TI - Neutralization of CXCL10 accelerates liver regeneration in carbon tetrachloride-induced acute liver injury VL - 40 SP - 191 KW - acute KW - alanine KW - animals KW - c57bl KW - carbon KW - cell KW - chemokine KW - cxcl10 KW - failure KW - female KW - file-import-08-07-27 KW - hepatocytes KW - inbred KW - liver KW - messenger KW - mice KW - neutralization KW - proliferation KW - proteins KW - recombinant KW - regeneration KW - rna KW - tests KW - tetrachloride KW - transaminase KW - up-regulation AU - Yoneyama, Hiroyuki AU - Kai, Yoshiro AU - Koyama, Jun AU - Suzuki, Kenji AU - Kawachi, Hiroshi AU - Narumi, Shosaku AU - Ichida, Takafumi PY - 2007/Dec// UR - http://dx.doi.org/10.1007/s00795-007-0371-x ER -