Inhibition of mechanical strain-induced fetal XXXX lung cell proliferation by @entity2287 , a stretch-activated channel blocker.

@entity11329 @entity62838 @entity141 @entity1855 @entity594 @entity515 @entity3365 @entity19643 @entity3411 @entity460 @entity18650 @entity35 @entity2287
Normal growth of the fetal lung is dependent upon fetal breathing movements. We have previously demonstrated that mechanical strain, simulating fetal breathing movements, stimulated DNA synthesis and cell division by reaggregated alveolar-like structures of fetal @entity35 lung cells. Herein, we report that both intracellular and extracellular @entity460 modulate strain-induced proliferative activity. Strain-induced cell proliferation was inhibited by @entity18650 /AM, an intracellular @entity460 chelator. The intracellular @entity460 modulators, @entity19643 and @entity62838 , increased DNA synthesis of unstrained cultures and partially reduced strain-induced cell growth activity. A similar effect was noted with the @entity460 ionophore @entity3365 . Extracellular @entity141 increased DNA synthesis in unstrained cultures in a concentration-dependent fashion. The stimulatory effect of strain on DNA synthesis was also dependent on the @entity460 concentration in the medium. Furthermore, strain-enhanced DNA synthesis was inhibited by the presence of a divalent ion chelator, EGTA, in the medium. Mechanical strain increased 45Ca2+ influx within 1 min after the onset of strain. This rapid entry of @entity460 was not affected by @entity460 channel blockers, such as @entity1855 or @entity3411 . @entity460 channel blockers @entity1855 , @entity594 , @entity3411 , @entity515 , or @entity11329 also did not inhibit strain-induced cell growth activity. In contrast, @entity2287 , a stretch-activated channel blocker, inhibited strain-induced 45Ca2+ influx and suppressed strain-enhanced DNA synthesis. We conclude that the entry of @entity460 into cells through stretch-activated ion channels plays a critical role in strain-induced fetal lung cell proliferation.
