title: Intercellular calcium waves mediate preferential cell growth toward the wound edge in polarized hepatic cells.
abstract: During liver regeneration, hepatocytes sense the damage and initiate proliferation of the quiescent cells through poorly understood mechanisms. Here, we have used cultured hepatic cells to study the roles played by intercellular calcium in mediating wound-healing processes. Well-differentiated and polarized Hep-G2 cells repaired an experimentally induced wound by induction of cell divisions. The resulting cellular growth did not occur evenly across the healing cell lawn; instead, proliferations were three times more active within 150-200 microm from the wound edge than further away; this periwound preferential cell growth was not observed in the poorly differentiated and/or nonpolarized cells. We have provided experimental evidence demonstrating that the wounding procedure itself could elicit a propagating calcium wave, and interestingly, blocking this injury-associated intercellular calcium communication could effectively inhibit the biased cell growth along the margin of the wound. A photolithography-based patterned cell culture system was employed to help delineate the mechanisms underlying this type of calcium signaling. In conclusion, our results suggested that intercellular communications via propagating calcium waves coordinate regenerative cell proliferations in response to hepatic tissue losses.
authors.affiliation: Institute of Anatomy and Cell Biology, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Yen-Jen
authors.initials: YJ
authors.lastname: Sung
authors.forename: Zulung
authors.initials: Z
authors.lastname: Sung
authors.forename: Chia-Lin
authors.initials: CL
authors.lastname: Ho
authors.forename: Ming-Te
authors.initials: MT
authors.lastname: Lin
authors.forename: Jih-Siang
authors.initials: JS
authors.lastname: Wang
authors.forename: Shun-Chun
authors.initials: SC
authors.lastname: Yang
authors.forename: Yann-Jang
authors.initials: YJ
authors.lastname: Chen
authors.forename: Chi-Hung
authors.initials: CH
authors.lastname: Lin
mesh_terms: D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects*; D002454:Cell Differentiation; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D016764:Cell Polarity / Q000187:drug effects; D004533:Egtazic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D006034:Glycyrrhetinic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D013498:Suramin / Q000494:pharmacology; D019284:Thapsigargin / Q000494:pharmacology; D014945:Wound Healing
chemical_list: C119129:18alpha-glycyrrhetinic acid; D004533:Egtazic Acid; D013498:Suramin; D019284:Thapsigargin; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D006034:Glycyrrhetinic Acid; D002118:Calcium