Intercellular calcium waves mediate preferential cell growth toward the wound edge in polarized hepatic cells

Yen Jen Sung, Zulung Sung, Chia Lin Ho, Ming Te Lin, Jih Siang Wang, Shun Chun Yang, Yann Jang Chen, Chi Hung Lin*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

33 Scopus citations


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 μm 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.

Original languageEnglish
Pages (from-to)209-218
Number of pages10
JournalExperimental Cell Research
Issue number2
StatePublished - 15 Jul 2003


  • Calcium wave
  • Microcontact printing
  • Proliferation
  • Wound healing


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