Matrine Suppresses Pancreatic Fibrosis by Regulating TGF-β/Smad Signaling in Rats
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Purpose: This study aimed to elucidate the molecular mechanisms of the anti-pancreatic fibrosis effects of matrine in rats. Materials and Methods: Trinitrobenzene sulfonic acid was administrated to rats to establish a pancreatic fibrosis model. Rats weredivided into four groups: Control, Sham, Model, and Matrine (n=8). Hematoxylin-eosin staining, Masson staining, and Azan stainingwere performed to evaluate pancreatic fibrosis. Expression of transforming growth factor-β1 (TGF-β1), α-smooth muscle actin(α-SMA), and collagen I in pancreatic tissues was evaluated by immunohistochemical staining. mRNA and protein levels of TGF-βreceptor 1 (TβR1), TβR2, and Smad2 in pancreatic tissues were determined by RT-PCR and Western blot, respectively. Results: In the model group, hyperplasia of glandules around the glandular ducts, mitochondrial swelling of acinous cells, andsevere fibrosis were found. Interestingly, in the Matrine group, mitochondrial swelling was only found in a small number of acinouscells, and the fundamental structures of pancreatic tissues were intact. Moreover, pancreatic fibrosis was markedly alleviated. Comparing to the Sham group, expression of α-SMA, TGF-β1, and collagen I was sharply elevated in the Model group (p<0.05);however, their expressions were much lower in the Matrine group, compared to the Model group (p<0.05). Compared with theSham group, mRNA and protein levels of Smad2, TβR1, and TβR2 in the Model group were notably raised (p<0.05). However,their high expression was significantly downregulated in the Matrine group (p<0.05). Conclusion: Matrine suppressed pancreatic fibrosis by regulating TGF-β/Smad signaling in rats.
Abstract
Purpose: This study aimed to elucidate the molecular mechanisms of the anti-pancreatic fibrosis effects of matrine in rats. Materials and Methods: Trinitrobenzene sulfonic acid was administrated to rats to establish a pancreatic fibrosis model. Rats weredivided into four groups: Control, Sham, Model, and Matrine (n=8). Hematoxylin-eosin staining, Masson staining, and Azan stainingwere performed to evaluate pancreatic fibrosis. Expression of transforming growth factor-β1 (TGF-β1), α-smooth muscle actin(α-SMA), and collagen I in pancreatic tissues was evaluated by immunohistochemical staining. mRNA and protein levels of TGF-βreceptor 1 (TβR1), TβR2, and Smad2 in pancreatic tissues were determined by RT-PCR and Western blot, respectively. Results: In the model group, hyperplasia of glandules around the glandular ducts, mitochondrial swelling of acinous cells, andsevere fibrosis were found. Interestingly, in the Matrine group, mitochondrial swelling was only found in a small number of acinouscells, and the fundamental structures of pancreatic tissues were intact. Moreover, pancreatic fibrosis was markedly alleviated. Comparing to the Sham group, expression of α-SMA, TGF-β1, and collagen I was sharply elevated in the Model group (p<0.05);however, their expressions were much lower in the Matrine group, compared to the Model group (p<0.05). Compared with theSham group, mRNA and protein levels of Smad2, TβR1, and TβR2 in the Model group were notably raised (p<0.05). However,their high expression was significantly downregulated in the Matrine group (p<0.05). Conclusion: Matrine suppressed pancreatic fibrosis by regulating TGF-β/Smad signaling in rats.
참고문헌 (29)
- Xue J, "Alternatively activated macrophages promote pancreatic fibrosis in chronic pancreatitis", Nat Commun, 6, pp.7158~ (2015)
- Tanaka K, "Significance of histopathological evaluation of pancreatic fibrosis to predict postoperative course after pancreatic surgery", Anticancer Res, 35, pp.1749~1756 (2015)
- Lu X, "Pathologic assessment of pancreatic fibrosis in predicting pancreatic fistula and management of prophylactic drain removal after pancreaticoduodenectomy", World J Surg, 40, pp.1520~1521 (2016)
- Nagathihalli NS, "Pancreatic stellate cell secreted IL-6 stimulates STAT3 dependent invasiveness of pancreatic intraepithelial neoplasia and cancer cells", Oncotarget, 7, pp.65982~65992 (2016)
- Tjomsland V, "The TGFβ-SMAD3 pathway inhibits IL-1αinduced interactions between human pancreatic stellate cells and pancreatic carcinoma cells and restricts cancer cell migration", J Exp Clin Cancer Res, 35, pp.122~ (2016)
- Tjomsland V, "Profile of MMP and TIMP expression in human pancreatic stellate cells : regulation by IL-1α and TGFβ and implications for migration of pancreatic cancer cells", Neoplasia, 18, pp.447~456 (2016)
- Xu L, "Puerarin, isolated from Pueraria lobata (Willd.), protects against hepatotoxicity via specific inhibition of the TGF-β1", Smad signaling pathway, thereby leading to anti-fibrotic effect, 2013, pp.20, 1172~1179
- Zhang YJ, "Effect of matrine on fibrosis of hypertrophy myocardium induced by pressure overload", Bull Sci Technol, 23, pp.67~71 (2007)
- Gao HY, "Hepatoprotective effect of Matrine salvianolic acid B salt on carbon tetrachloride-induced hepatic fibrosis", J Inflamm(Lond), 9, pp.16~ (2012)
- Zhang HW, "Renoprotective effects of matrine on experimental glomerulosclerosis in rats", Zhonghua Er Ke Za Zhi, 42, pp.737~740 (2004)
- Yuan X, "Effect of matrine on NF-кB and collagen protein Ⅲ of rats with pulmonary fibrosis", J Xinxiang Med College, 26, pp.327~330 (2009)
- Bikádi P, "Internal positive controls of alpha-smooth muscle actin(α-SMA)in bovine tissues Immunohistochemical study", Magyar Allatorvosok Lapja, 137, pp.151~158 (2015)
- Meng LP, "The correlation of magnetic resonance perfusion parameters and CD34, a-SMA of liver fibrosis and cirrhosis in rats", Radiol Pract, 31, pp.580~585 (2016)
- Hu GX, "Effects of hydroxycamptothecin on TGFb1, a-SMA and collagen I expression in rat hepatic satellite cells", Zhonghua Gan Zang Bing Za Zhi, 20, pp.453~457 (2012)
- De Jesus Araújo L, "Evaluation of MMP-1, MMP-10, TIMP-1, a-SMA and TGF-b1 in angiofibromas of tuberous sclerosis", Minerva Stomatol, 60, pp.25~33 (2011)
- David CJ, "TGF-βtumor suppression through a lethal EMT", Cell, 164, pp.1015~1030 (2016)
- Zhang H, "TGF-β inhibition rescues hematopoietic stem cell defects and bone marrow failure in Fanconi anemia", Cell Stem Cell, 18, pp.668~681 (2016)
- Yan X, "Smad7 protein interacts with receptor-regulated Smads(R-Smads)to inhibit transforming growth factor-β(TGF-β)", Smad signaling, 2016, pp.291, 382~392
- Da C, "Nobiletin inhibits epithelialmesenchymal transition of human non-small cell lung cancer cells by antagonizing the TGF-β1", Smad3 signaling pathway, 2016, pp.35, 2767~2774
- Ma M, "MiR-487a promotes TGF-β1-induced EMT, the migration and invasion of breast cancer cells by directly targeting MAGI2", Int J Biol Sci, 12, pp.397~408 (2016)
- Zhang YB, "Dimeric matrine-type alkaloids from the roots of Sophora flavescens and their anti-epatitis B virus activities", J Org Chem, 81, pp.6273~6280 (2016)
- Zhou Y, "The alkaloid matrine of the root of Sophora flavescens prevents arrhythmogenic effect of ouabain", Phytomedicine, 21, pp.931~935 (2014)
- Sun N, "Matrine displayed antiviral activity in porcine alveolar macrophages co-infected by porcine reproductive and respiratory syndrome virus and porcine circovirus type 2", Sci Rep, 6, pp.24401~ (2016)
- Pu J, "Matrine exerts a strong anti-arthritic effect on type II collagen-induced arthritis in rats by inhibiting inflammatory responses", Int J Mol Sci, 17, pp.1410~ (2016)
- Liu Z, "GW27-e1128 Matrine inhibits cardiac fibrosis by inhibiting TGFβ1", smad signaling pathway, 2016, pp.68(16 Suppl), C40~
- Mihailova S, "A study of TNF-α, TGF-β, IL-10, IL-6, and IFN-γgene polymorphisms in patients with depression", J Neuroimmunol, 293, pp.123~128 (2016)
- Yang P, "Regulation of fibroblasts proliferation and function of human hypertrophic scar by Oxymatrine through TGF-β signaling pathway", Chin J Aesth Plast Surg, 21, pp.557~559 (2010)
- Zhang Y, "Matrine suppresses cardiac fibrosis by inhibiting the TGF-β", Smad pathway in experimental diabetic cardiomyopathy, 2018, pp.17, 1775~1781
- Zhao N, "TGF-β", Smads signal pathway is involved in the anti-fibrotic effect of matrine and improvement of the cardiac function in the diabetic cardiomyopathy rats, 2015, pp.13, 312~327
