Key result
Mechanical stretch transiently increases fibroblast stiffness and MRLC diphosphorylation via the RhoA signaling cascade.
Why the study?
Does mechanical stretch regulate cellular contractile force via diphosphorylation of MRLC and RhoA signaling in fibroblasts?
Does mechanical stretch regulate cellular contractile force via diphosphorylation of MRLC and RhoA signaling in fibroblasts?
Cellular contractile force in response to mechanical stretch is regulated by the diphosphorylation and dephosphorylation of myosin regulatory light chain via the RhoA signaling cascade.
Supports RhoA-mediated fibroblast stiffening under stretch; leaves open relevance to cardiac remodeling or fibrosis.
Fibroblasts regulate their contractile force in response to external stretch; however, the detailed mechanism by which the force is regulated is unclear. Here, we show that diphosphorylation and dephosphorylation of myosin regulatory light chain (MRLC) are involved in the stretch-induced force response. Cellular stiffness, which reflects the cellular contractile force, under external stretch was measured by mechanical-scanning probe microscopy. Fibroblasts (NIH-3T3) expressing green fluorescent protein (GFP)-tagged mutant-type MRLC (MRLC(T18A)-GFP), which cannot be diphosphorylated, did not show any stretch-induced stiffness response, whereas the stiffness in cells expressing GFP-tagged wild-type MRLC (MRLC(WT)-GFP) increased immediately after the stretch and subsequently decreased after 1-2 h. Urea-PAGE western blot analysis showed that the proportion of diphosphorylated MRLC (PP-MRLC) transiently increased after the stretch and decreased after 1-2 h. Dominant-negative RhoA (RhoA(N19))-expressing cells did not show the stiffness response to the stretch, whereas wild-type RhoA-expressing cells did. It was concluded that the cellular force response originates in the stretch-induced diphosphorylation and dephosphorylation of MRLC and is regulated via the RhoA signaling cascade.
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Mizutani et al. (2009) studied this question. Mechanical stretch vs. Mutant-type MRLC or dominant-negative RhoA expressing cells was evaluated on Cellular stiffness and proportion of diphosphorylated MRLC. Mechanical stretch induced a transient increase in cellular stiffness and diphosphorylation of myosin regulatory light chain in fibroblasts, regulated via the RhoA signaling cascade.
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