Involvement of eIF6 in external mechanical stretch-mediated murine dermal fibroblast function via TGF-β1 pathway.
External mechanical loading on a wound commonly increases fibrosis. Transforming growth factor-β1 (TGF-β1) has been implicated in fibrosis in various models, including the mechanical force model. However, the underlying mechanism is unclear. Our previous experiments suggested that eukaryotic initiation factor 6 (eIF6) acted as a regulator of TGF-β1 expression, and negatively impact on collagen synthesis. Our current results showed that external mechanical stretching significantly increased COL1A1, TGF-β1 and eIF6 expression as well as dermal fibroblasts proliferation, both in vitro and in vivo. eIF6 -deficient (eIF6+/-) cells exhibited significantly higher levels of COL1A1, and these levels increased further with external mechanical stretching, suggesting that mechanical stretching plays a synergistic role in promoting COL1A1 expression in eIF6+/-cells. Inhibition of TGFβR I/II by LY2109761 decreased COL1A1 protein expression in eIF6+/-dermal fibroblasts in a cell stretching model, and attenuated granulation tissue formation in partial thickness wounds of eIF6+/-mice. These data suggest that mechanical stretching has a synergistic role in the expression of COL1A1 in eIF6+/-cells, and is mediated by activation of TGFβRI/II. Taken together, our results indicate that eIF6 may be involved in external mechanical force-mediated murine dermal fibroblast function at least partly through the TGF-β1 pathway.
Institute of Burn Research, State Key Laboratory of Trauma, Burn and Combined Injury, Southwest Hospital, The Third Military Medical University, Chongqing, 400038, People's Republic of China.|Nursing Department, The Third Military Medical University, Chongqing, 400038, People's Republic of China.
Qin
Q
Shu
Institute of Burn Research, State Key Laboratory of Trauma, Burn and Combined Injury, Southwest Hospital, The Third Military Medical University, Chongqing, 400038, People's Republic of China.|Chongqing Key Laboratory for Disease Proteomics, The Third Military Medical University, Chongqing, 400038, China.
Jianglin
J
Tan
Department of Rehabilitation Sciences and Physiotherapy, University of Antwerp, Belgium.
Van Daele
VD
Ulrike
Institute of Burn Research, State Key Laboratory of Trauma, Burn and Combined Injury, Southwest Hospital, The Third Military Medical University, Chongqing, 400038, People's Republic of China.|Chongqing Key Laboratory for Disease Proteomics, The Third Military Medical University, Chongqing, 400038, China.
Xiaorong
X
Zhang
Institute of Burn Research, State Key Laboratory of Trauma, Burn and Combined Injury, Southwest Hospital, The Third Military Medical University, Chongqing, 400038, People's Republic of China.|Department of Urology, Second Affiliated Hospital, Third Military Medical University, Chongqing, 400037, People's Republic of China.
Jiacai
J
Yang
Institute of Burn Research, State Key Laboratory of Trauma, Burn and Combined Injury, Southwest Hospital, The Third Military Medical University, Chongqing, 400038, People's Republic of China.|Chongqing Key Laboratory for Disease Proteomics, The Third Military Medical University, Chongqing, 400038, China.
Sisi
S
Yang
Institute of Burn Research, State Key Laboratory of Trauma, Burn and Combined Injury, Southwest Hospital, The Third Military Medical University, Chongqing, 400038, People's Republic of China.|Chongqing Key Laboratory for Disease Proteomics, The Third Military Medical University, Chongqing, 400038, China.
Xiaohong
X
Hu
Institute of Burn Research, State Key Laboratory of Trauma, Burn and Combined Injury, Southwest Hospital, The Third Military Medical University, Chongqing, 400038, People's Republic of China.|Chongqing Key Laboratory for Disease Proteomics, The Third Military Medical University, Chongqing, 400038, China.
Weifeng
W
He
Institute of Burn Research, State Key Laboratory of Trauma, Burn and Combined Injury, Southwest Hospital, The Third Military Medical University, Chongqing, 400038, People's Republic of China.|Chongqing Key Laboratory for Disease Proteomics, The Third Military Medical University, Chongqing, 400038, China.
Gaoxing
G
Luo
Institute of Burn Research, State Key Laboratory of Trauma, Burn and Combined Injury, Southwest Hospital, The Third Military Medical University, Chongqing, 400038, People's Republic of China.|Chongqing Key Laboratory for Disease Proteomics, The Third Military Medical University, Chongqing, 400038, China.
Jun
J
Wu
D000818:Animals; D049109:Cell Proliferation; D005347:Fibroblasts / Q000502:physiology*; D051379:Mice; D010448:Peptide Initiation Factors / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism*; D013314:Stress, Mechanical; D013312:Stress, Physiological; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
C115811:Itgb4bp protein, mouse; D010448:Peptide Initiation Factors; D018125:Receptors, Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II