Role of TGF-β1/Smad3 Signaling Pathway in Secretion of Type I and III Collagen by Vascular Smooth Muscle Cells of Rats Undergoing Balloon Injury

Abstract

Antisense Smad3 adenoviral vectors were used to transfect vascular smooth muscle cells (VSMCs) from rats with balloon injury or infused into the rat balloon-catheter injured carotid arteries, and the role of TGF-β1/Smad3 signaling pathway in the secretion of type I and III collagen by VSMCs following balloon injury was investigated. Antisense Smad3 adenoviral vectors were used to transfect these VSMCs (antisense Smad3 group). A total 90 rats were randomly assigned into blank control group, experiment group, negative control group. In the in vitro study, the expression of type I and III collagen was markedly reduced in the antisense Smad3 group when compared with the control groups (P < 0.05). In the in vivo study, the expression of type I and III collagen was significantly lower than that in the negative control group at 3 days, 1 week and 2 weeks after injury (P < 0.05). At 2 weeks and 3 months after injury, the lumen area in the antisense Smad3 group was markedly increased but the intimal area dramatically reduced when compared with the negative control (P < 0.05). We conclude that transfection of VSMCs with antisense Smad3 can reduce the secretion of type I and III collagen which then inhibit intimal hyperplasia.

Lentiviral Vector‐Mediated FoxO1 Overexpression Inhibits Extracellular Matrix Protein Secretion Under High Glucose Conditions in Mesangial Cells

“…Phosphorylation of Smad3 by active TGF‐βRI leads to complex formation with Smad4, followed by nuclear translocation [Shi and Massague, ; Massague, ]. After releasing from the complex, Smad3 binds to the promoter, associates with other transcription factors, and initiates the transcription of target genes [Das et al, ; Lu et al, ]. Our results illustrated that both 3A‐FoxO1 and SiRNA‐FoxO1 did not affect Smad3 expression levels, whereas high‐glucose‐induced elevation of p‐Smad3 protein was decreased after overexpression of 3A‐FoxO1.…”

Hyperammonaemia induces hepatic injury with alteration of gene expression profiles

“…A class of anti-stimulus signalling cascades would then be triggered, accompanied with cellular functions, such as proliferation, apoptosis, differentiation and migration, are regulated. One DE gene of Smad3 (28)(29)(30)(31) in our study (Table S2), is an important component of the TGF-b signalling pathway, regulating a wide spectrum of cellular functions. Matsubara et al (31) concluded that the TGF-b-Smad3 signalling pathway mediates hepatic bile acid and phospholipid metabolism following lithocholic acid-induced liver injury.…”

“…A class of anti‐stimulus signalling cascades would then be triggered, accompanied with cellular functions, such as proliferation, apoptosis, differentiation and migration, are regulated. One DE gene of Smad3 in our study (Table S2), is an important component of the TGF‐β signalling pathway, regulating a wide spectrum of cellular functions. Matsubara et al .…”

Enhanced neointimal fibroblast, myofibroblast content and altered extracellular matrix composition: Implications in the progression of human peripheral artery restenosis

“…Furthermore, resident neointimal SMCs and stellate cells will enhance neointimal collagen content. Therefore, neointimal fibroblast and myofibroblast may be crucial in type III collagen synthesis, leading to neointimal expansion [23,24]. These cells were extensively studied previously in coronary artery restenosis [25–29].…”