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The effect of Smad2- and Smad3-targeting RNA interference on extracellular matrix synthesis in rat fibroblasts of peritoneal adhesion tissues.

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机构： [1]Department of Pharmaceutical Science, School of Medical Engineering, Foshan University, Foshan, Guangdong, China [2]Department of Pharmaceutical Science, Medical College of Shaoguan University, Shaoguan, Guangdong, China [3]Department of Traditional Chinese Pharmaceutics, School of Traditional Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou, Guangdong, China [4]Guangdong Provincial Key Laboratory of Pharmaceutical Bioactive Substances and School of Basic Medicine, Guangdong Pharmaceutical University, Guangzhou, Guangdong, China [5]Department of Pharmacy, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.

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关键词： TGF-β/Smads peritoneal adhesions fibroblast small interference RNA (siRNA)

摘要：

Fibroblasts migrating to peritoneum injuries play an important role in the development of postoperative peritoneal adhesions due to the excessive synthesis and deposition of extracellular matrix (ECM). This effect is mainly induced by the transforming growth factor-β (TGF-β). Studies indicate that elevated TGF-β1 levels and TGF-β1/Smad signaling are both implicated in the formation of peritoneal adhesions. To confirm the effect of TGF-β1/Smad signaling interference in regulating excessive ECM synthesis, a total of four different R-Smad-targeting small interference RNA (siRNA) duplexes (Smad2-500, Smad2-956, Smad3-378, Smad3-1385) were tested in this study using a TGF-β1-stimulated adhesion tissue fibroblasts (ATFs) cell model. The in vitro assessments show that all proposed siRNAs are capable of significantly downregulating the mRNA and protein levels of Smad2 and Smad3 in ATFs. They also inhibit the phosphorylation of both Smads, which confirms their effect in blocking the TGF-β1/Smad signaling pathway. Moreover, the siRNA duplexes can appreciably lower the elevated levels of fibronectin and collagen 3 alpha 1 (COL3A1) in TGF-β1-stimulated ATFs, and the Smad3-378 siRNA can actually restore both molecules (fibronectin and COL3A1) to normal levels. Therefore, the Smad3-378 siRNA is suitable for both adhesion prevention and wound healing. Overall, our results indicate that postoperative adhesion prophylaxis may be achieved by temporarily blocking TGF-β1/Smad signaling transduction. AJTR Copyright © 2020.

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出版当年[2019]版：

大类 | 3 区医学

小类 | 3 区医学：研究与实验 4 区肿瘤学

最新[2025]版：

大类 | 4 区医学

小类 | 4 区医学：研究与实验 4 区肿瘤学

第一作者：

第一作者机构： [1]Department of Pharmaceutical Science, School of Medical Engineering, Foshan University, Foshan, Guangdong, China [*2]Department of Pharmaceutical Scien-ce, School of Medical Engineering, Foshan Univer-sity, No. 5 Hebin Road, Chancheng District, Foshan 528000, Guangdong, China.

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通讯作者：

通讯机构： [1]Department of Pharmaceutical Science, School of Medical Engineering, Foshan University, Foshan, Guangdong, China [3]Department of Traditional Chinese Pharmaceutics, School of Traditional Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou, Guangdong, China [*1]Department of Traditional Chinese Pharmaceutics, School of Traditional Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou Higher Edu-cation Mega Center, Guangzhou 510006, Guang-dong, China. [*2]Department of Pharmaceutical Scien-ce, School of Medical Engineering, Foshan Univer-sity, No. 5 Hebin Road, Chancheng District, Foshan 528000, Guangdong, China.

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The effect of Smad2- and Smad3-targeting RNA interference on extracellular matrix synthesis in rat fibroblasts of peritoneal adhesion tissues.

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