Reactive Oxygen Species Mediate Bi‐axial Strain‐Induced Fibroblast Proliferation

Mechanical force modulates fundamental short‐ and long‐term responses in various cell types. We sought to define a mechanism for rat abdominal wall musculo‐tendon fibroblast (abMTF) proliferative response during biaxial cyclic strain (BCS). abMTF were subjected to BCS (10%; 0.2 Hz) in the presence of 2.5–5% FBS up to 6 days. Proliferation of abMTF in response to BCS was measured by direct cell counts. BCS stimulated abMTF proliferation in a time dependent manner compared with control. Increased proliferation depended on the concentration of FBS, with no BCS‐induced proliferative response when cultured in 1% FBS. BCS‐induced proliferative response was blocked by selective MAPK inhibitor PD98059 (50 μM) with inhibiting BCS induced rapid ERK1/2 phosphorylation. Further, BCS‐induced MAPK activation and proliferation was inhibited in the presence of antioxidants, 1% DMSO, 5 μM ebselen and 25μM resveratrol, respectively. H 2 O 2 (3–300 μM), exogenous reactive oxygen species (ROS), stimulated abMTF proliferation and ERK1/2 phosphorylation in a dose‐dependent manner. Antioxidant treatment inhibited BCS‐induced intracellular ROS production detected by DCF fluorescence, while 300 μM H 2 O 2 stimulated abMTF proliferation and ERK1/2 phosphorylation. These results suggest that BCS‐induced abMTF proliferation depends on a MAPK/ERK pathway mediated by intracellular ROS in response to mechanical force.