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. 2016 Feb 16:6:21112.
doi: 10.1038/srep21112.

Mechanical stretching stimulates collagen synthesis via down-regulating SO2/AAT1 pathway

Jia Liu  1 , Wen Yu  1 , Yan Liu  2 , Selena Chen  3 , Yaqian Huang  1 , Xiaohui Li  4 , Cuiping Liu  5 , Yanqiu Zhang  6 , Zhenzhen Li  1 , Jie Du  2   7 , Chaoshu Tang  8   9 , Junbao Du  1   9 , Hongfang Jin  1   2
Affiliations

Mechanical stretching stimulates collagen synthesis via down-regulating SO2/AAT1 pathway

Jia Liu et al. Sci Rep. .

Abstract

The aim of the study was to investigate the role of endogenous sulfur dioxide (SO2)/ aspartate aminotransferase 1 (AAT1) pathway in stretch-induced excessive collagen expression and its mechanism. The mechanical stretch downregulated SO2/AAT1 pathway and increased collagen I and III protein expression. Importantly, AAT1 overexpression blocked the increase in collagen I and III expression, transforming growth factor-β1 (TGF- β1) expression and phosphorylation of Smad2/3 induced by stretch, but AAT1 knockdown mimicked the increase in collagen I and III expression, TGF- β1 expression and phosphorylation of Smad2/3 induced by stretch. Mechanistically, SB431542, a TGF-β1/Smad2/3 inhibitor, eliminated excessive collagen I and III accumulation induced by AAT1 knockdown, stretch or stretch plus AAT1 knockdown. In a rat model of high pulmonary blood flow-induced pulmonary vascular collagen accumulation, AAT1 expression and SO2 content in lung tissues of rat were reduced in shunt rats with high pulmonary blood flow. Supplement of SO2 derivatives inhibited activation of TGF- β1/Smad2/3 pathway and alleviated the excessive collagen accumulation in lung tissues of shunt rats. The results suggested that deficiency of endogenous SO2/AAT1 pathway mediated mechanical stretch-stimulated abnormal collagen accumulation via TGF-β1/Smad2/3 pathway.

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Figures

Figure 1
Figure 1. Stretch inhibited the SO2/AAT1 pathway and enhanced collagen remodeling in PAFs.
The cells were stretched at 60 cycles/min, 1 Hz, and 20% elongation for 24 hours. (a) The effect of mechanical stretching on the SO2/AAT1 pathway. (b) The effect of mechanical stretching on collagen. *P < 0.05, data are presented as mean ± SD (n = 5), and two-sample independent t test was used.
Figure 2
Figure 2. Overexpression of AAT1 prevented collagen remodeling and inhibited the activation of the TGF-β1/Smad2/3 pathway in PAFs.
(a) The effect of AAT1 overexpression on the SO2/AAT1 pathway. (b) The effect of AAT1 overexpression on collagen remodeling. (c) The effect of AAT1 overexpression on the TGF-β1/Smad2/3 pathway. *P < 0.05, data are presented as mean ± SD (n = 5) and ANOVA followed by post-hoc analysis was used. AAT1: AAT1 overexpression.
Figure 3
Figure 3. Knockdown of AAT1 augmented collagen remodeling and activated the TGF-β1/Smad2/3 pathway in PAFs.
(a) The effect of AAT1 knockdown on the SO2/AAT1 pathway. (b) The effect of AAT1 knockdown and SB431542 on collagen remodeling and the TGF-β1/Smad2/3 pathway. *P < 0.05, data are presented as mean ± SD (n = 5) and ANOVA followed by post-hoc analysis was used. AAT1sh: AAT1 knockdown. SB431542: a TGF-β1/Smad2/3 inhibitor, concentration of 5 μmol/L.
Figure 4
Figure 4. The level of SO2/AAT1 pathway and the expression of collagen and TGF-β1/Smad2/3 pathway in rats.
(a) The expression of AAT1 and the concentration of SO2. (b) The effect of SO2 derivatives on collagen remodeling. (c) The effect of SO2 derivatives on the TGF-β1/Smad2/3 pathway. *P < 0.05, data are presented as mean ± SD (n = 8) and ANOVA followed by post-hoc analysis was used.
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References

    1. Rosenzweig E. B. & Barst R. J. Congenital heart disease and pulmonary hypertension: pharmacology and feasibility of late surgery. Prog. Cardiovasc. Dis. 55, 128–133 (2012). - PubMed
    1. Baumbach G. L. & Heistad D. D. Remodeling of cerebral arterioles in chronic hypertension. Hypertension. 13, 968–972 (1989). - PubMed
    1. Gibbons G. H. & Dzau V. J. The emerging concept of vascular remodeling. N. Engl. J. Med. 330, 1431–1438 (1994). - PubMed
    1. Bradley J. M. et al. Effects of mechanical stretching on trabecular matrix metalloproteinases. Invest. Ophthalmol. Vis. Sci. 42, 1505–1513 (2001). - PubMed
    1. Godin D., Ivan E., Johnson C., Magid R. & Galis Z. S. Remodeling of carotid artery is associated with increased expression of matrix metalloproteinases in mouse blood flow cessation model. Circulation. 102, 2861–2866 (2000). - PubMed

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