Mechanotransduction and intracellular signaling mechanisms of stretch-induced remodeling in endothelial cells

Masahiro Sokabe, Keiji Naruse, Shorei Sai, Takako Yamada, Keisuke Kawakami, Masumi Inoue, Kichiro Murase, Motoi Miyazu

Research output: Contribution to journalArticlepeer-review

39 Citations (Scopus)

Abstract

We investigated the signaling mechanism of stretch-induced cell remodeling in human umbilical vein endothelial cells (HUVECs). Freshly dissociated HUVECs were cultured on an elastic silicon membrane and subjected to uniaxial cyclic stretch (20% in length, 1 Hz). The cells started to change their morphology as early as 15 min after stretch onset, and most cells eventually aligned perpendicularly to the stretch axis within 1 h. This remodeling was dependent on the increase in intracellular calcium concentration ([Ca2+](i)) via a Ca2+-permeable stretch-activated (SA) channel. During the process of remodeling, extensive rearrangement of stress fibers and focal adhesions was observed, which may be close to the final step in the intracellular signaling cascade. This event was [Ca2+](i)-dependent, suggesting the existence of a Ca2+-dependent intermediate cascade that links [Ca2+](i) to the rearrangement of cytoskeletons and focal adhesions. We found that some proteins, including ppl25(FAK) (focal adhesion kinase) and paxillin, were tyrosine phosphorylated during cyclic stretch in a Ca2+-dependent manner. Inhibition of this tyrosine phosphorylation prohibited the stretch-dependent rearrangement of cytoskeletons and focal adhesions as well as the remodeling. Finally the tyrosine kinase src, which could phosphorylate pp125(FAK) was found to be activated in a [Ca2+](i)-dependent way during stretch. All of the above molecular events were consistently Ca2+-dependent, which led us to propose the signaling cascade: SA channel activation → [Ca2+](i) increase → src activation → protein tyrosine phosphorylation → rearrangement of cytoskeletons and focal adhesions → cell remodeling.

Original languageEnglish
Pages (from-to)191-193
Number of pages3
JournalHeart and Vessels
Volume12
Issue numberSUPPL. 12
Publication statusPublished - 1997
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

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