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. 2021 Feb 12;118(2):440–460. doi: 10.1093/cvr/cvab035

Table 2.

Immediate responses of signalling molecules in fibroblasts to stretch

Response Main findings Cell type Coating and plate Stretch machine Stretch pattern Stretch duration Serum Reference
Immediate early gene activation Quick and transient phosphorylation of c-fos NRVF Collagen-coated silicone membrane Homemade stretch device 20% uniaxial 24 h Serum-free Sadoshima et al., (1992)132
ERK2 and JNK1 activated by stretch in matrix-dependent manner. Stretch-conditioned medium also activated ARVF Collagen, laminin, vitronectin, and fibronectin Modified from Lee et al., 1996131 4% static equibiaxial 1, 5, 10 min NS MacKenna et al., (1998)55
G-proteins activated by 1 min of stretch, several GTP-binding response depending on stretch pattern Adult male RCF Collagen I-coated silicone elastic membrane Modified from Lee et al., 1996131 5-s, 10-s, or 60-s stretch, 3% or 6% equibiaxial 5–60 s 10% FBS Gudi et al., (1998)106
C-fos and fra-1 mRNA increased. C-Jun mRNA unchanged NRVF Collagen I-coated flexible plate Flexercell 15% biaxial static stretch 0–60 min Serum-free Van Wamel et al., (2000)93
P38-phosphorylation increased ARVF Collagen I, plasma fibronectin, or fibronectin ED-A domain peptide-coated magnetite beads Ceramic permanent magnet Static force perpendicular to cell surface 15 min to 8 h Serum-free Wang et al., (2000)112
ERK and p38 phosphorylation increased NRVF Collagen I-coated magnetite beads Ceramic permanent magnet Static force perpendicular to cell surface 0.5, 1, 2, and 4 h Serum-free Wang et al., (2003)68
MAPK activated in time-dependent and coating-dependent manner; greater and faster on collagen and charged membrane Neonatal RCF Fibronectin-, laminin-, collagen-coated; uncoated charged silicone elastic membrane Modified from Yost et al., 2000101 0.08 Hz, 5% uniaxial 1, 5, and 10 min 10% NBS + 5% FBS Atance et al., (2004)86
ERK1/2 and p38 phosphorylation increased Foetal RCF Elastin-coated Flex-I plate Flexercell FX-3000 1.5 Hz, 20% From 10 min to 24 h 10% FBS Papakrivopoulou et al., (2004)105

Rapid and transient phosphorylation of JNK. Long-term stable phosphorylation of p38 (4–24 h).

p38α increased angiotensinogen expression; JNK1/2 phosphorylation decreased it

NRVF Collagen IV-coated BioFlex plate Flexercell FX-3000 20% equiaxial static stretch 2–30 min and 1–24 h Serum-free Lal et al., (2008)115
Stretch activated Rac1 and RhoA within 5 min. Rac1 activity returned to control after 4 h; RhoA remained high throughout 24 h of stretch. Rac1 inhibited angiotensin expression through JNK-dependent and independent mechanisms; RhoA stimulated it through p38-dependent mechanism NRVF Collagen IV-coated BioFlex plate Flexercell FX-3000 20% equiaxial static stretch From 2 min to 24 h Serum-free Verma et al., (2011)116

ARVF, adult rat ventricular fibroblasts; ERK, extracellular signal-regulated kinase; FBS, foetal bovine serum; JNK, c-Jun N-terminal kinase; MAPK, mitogen-activated protein kinase; NBS, newborn bovine serum; NRVF, neonatal rat ventricular fibroblasts; NS, not stated; p38,  p38 mitogen-activated protein kinase; Rac1, Ras-related C3 botulinum-toxin substrate-1; RCF, rat cardiac fibroblasts; RhoA, Ras homolog family member A.