• Korean Journal of Radiology
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• v.21 no.5
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• pp.588-597
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• 2020

Objective: To investigate the value of combined chemical exchange saturation transfer (CEST) and conventional magnetization transfer imaging (MT) in detecting metabolic and structural changes of renal fibrosis in rats with unilateral ureteral obstruction (UUO) at 3T MRI. Materials and Methods: Thirty-five Sprague-Dawley rats underwent UUO surgery (n = 25) or sham surgery (n = 10). The obstructed and contralateral kidneys were evaluated on days 1, 3, 5, and 7 after surgery. After CEST and MT examinations, ¹⁸F-labeled fluoro-2-deoxyglucose positron emission tomography was performed to quantify glucose metabolism. Fibrosis was measured by histology and western blots. Correlations were compared between asymmetrical magnetization transfer ratio at 1.2 ppm (MTR_asym(1.2ppm)) derived from CEST and maximum standard uptake value (SUV_max) and between magnetization transfer ratio (MTR) derived from MT and alpha-smooth muscle actin (α-SMA). Results: On days 3 and 7, MTR_asym(1.2ppm) and MTR of UUO renal cortex and medulla were significantly different from those of contralateral kidneys (p < 0.05). On day 7, MTR_asym(1.2ppm) and MTR of UUO renal cortex and medulla were significantly different from those of sham-operated kidneys (p < 0.05). The MTR_asym(1.2ppm) of UUO renal medulla was fairly negatively correlated with SUV_max (r = -0.350, p = 0.021), whereas MTR of UUO renal medulla was strongly negatively correlated with α-SMA (r = -0.744, p < 0.001). Conclusion: CEST and MT could provide metabolic and structural information for comprehensive assessment of renal fibrosis in UUO rats in 3T MRI and may aid in clinical monitoring of renal fibrosis in patients with chronic kidney disease.

• Tuberculosis and Respiratory Diseases
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• v.79 no.3
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• pp.143-152
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• 2016

Background: Idiopathic pulmonary fibrosis (IPF) is a progressive and lethal lung disease characterized by the accumulation of excessive fibroblasts and myofibroblasts in the extracellular matrix. The transforming growth factor ${\beta}1$ (TGF-${\beta}1$)-induced epithelial-to-mesenchymal transition (EMT) is thought to be a possible source of fibroblasts/myofibroblasts in IPF lungs. We have previously reported that apolipoprotein A1 (ApoA1) has anti-fibrotic activity in experimental lung fibrosis. In this study, we determine whether ApoA1 modulates TGF-${\beta}1$-induced EMT in experimental lung fibrosis and clarify its mechanism of action. Methods: The A549 alveolar epithelial cell line was treated with TGF-${\beta}1$ with or without ApoA1. Morphological changes and expression of EMT-related markers, including E-cadherin, N-cadherin, and ${\alpha}$-smooth muscle actin were evaluated. Expressions of Smad and non-Smad mediators and TGF-${\beta}1$ receptor type 1 ($T{\beta}RI$) and type 2 ($T{\beta}RII$) were measured. The silica-induced lung fibrosis model was established using ApoA1 overexpressing transgenic mice. Results: TGF-${\beta}1$-treated A549 cells were changed to the mesenchymal morphology with less E-cadherin and more N-cadherin expression. The addition of ApoA1 inhibited the TGF-${\beta}1$-induced change of the EMT phenotype. ApoA1 inhibited the TGF-${\beta}1$-induced increase in the phosphorylation of Smad2 and 3 as well as that of ERK and p38 mitogen-activated protein kinase mediators. In addition, ApoA1 reduced the TGF-${\beta}1$-induced increase in $T{\beta}RI$ and $T{\beta}RII$ expression. In a mouse model of silica-induced lung fibrosis, ApoA1 overexpression reduced the silica-mediated effects, which were increased N-cadherin and decreased E-cadherin expression in the alveolar epithelium. Conclusion: Our data demonstrate that ApoA1 inhibits TGF-${\beta}1$-induced EMT in experimental lung fibrosis.