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Objective: To study the changes of TGFβ/Smad signaling expression in oral squamous cell carcinoma (OSCC) after hyperthermia. Methods: The expression of TGFβ, Smad2, 3, 4 and 7 in OSCC of tumor bearing nude mice were examined by quantitative real-time RT-PCR and Western blot respectively. Results: The mRNA expression of TGFβ, Smad2 and 3 was decreased significantly, and the mRNA levels of Smad7 was elevated in hyperthermia (HT) group (n = 10) (P ＜ 0. 05), but the mRNA expression of Smad4 did not change significantly compared with that of control group (n = 10) . The changes of protein expression of TGFβ, Smad7 and 4 were consistent with that of mRNA, the expression of Smad2 and 3 was not significantly different between the groups, but the expression of p Smad2 and p Smad3 decreased dramatically in HT group (P ＜ 0. 05) . Conclusion: TGFβ/Smad signaling exhibits important role in the antitumor effects of hyperthermia, and the inhibition of Smad7 on R-Smad phosphorylation may play a key role.
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Liver fibrosis is a tissue repair compensatory response to liver injury caused by various chronic factors, ultimately leading to liver cirrhosis, liver failure and even hepatocellular carcinoma. Abnormal activation of hepatic stellate cells is the cellular basis of liver fibrosis development. Pepstatin Pr, the derivative of pepstatin A, was isolated from Streptomyces sp. CPCC 202950. Our purpose was to investigate the anti-fibrotic activity of pepstatin Pr and explore its molecular mechanism. Hepatic stellate cell LX-2 was stimulated by TGFβ1 and sub- sequently treated with pepstatin Pr. Its cytotoxicity was detected by sulforhodamine B (SRB) assay. The expression of COL1A1, α-SMA and cathepsin D, signaling proteins TGFβ, Smad and YAP/TAZ were detected by Western blot or real-time PCR. The results showed that pepstatin Pr was not cytotoxic to LX-2 cells. And pepstatin Pr significantly reduced the mRNA and protein expression of COL1A1 and α-SMA, which are important liver fibrosis markers. Pepstatin Pr also repressed the protein expression level of cathepsin D, TGFβ1, YAP/TAZ, the phospholation level of Smad2, and YAP nuclear translocation. In conclusion, pepstatin Pr exhibits anti-fibrotic effects in TGFβ1-stimulaed LX-2 cells by mediating YAP-TGFβ-Smad pathway.
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Objective To study the effect of OK on the differentiation of bone marrow stromal stem cells (BMSCs) through the TGFβ/Smad signaling pathway in rats. Methods We removed the bilateral ovaries of rats to replicate OP model, and isolated and cultured BMSCs. BMSCs isolated from nomal rats were cultured as control group, BMSCs isolated from OP rats were divided into 5 groups, OP model group was regularly cultured, positive control group was treated with alendronate sodium (1 μmol/L), low, medium and high OK treatment group were treated with 50 mL/L, 100 mL/L and 200 ml/L OK respectively.After 24 h incubation, all cells were collected. The proliferation rate of BMSCs was determined by MTT method, and ELISA method was employed to detect the contents of bone formation markers, RT-qPCR was used to determine the m RNA expression level of TGFβ and the protein expression levels of TGFβ, p-Smad2/3 and of Smad2/3 were detected by Western blot. Results Compared with control group, the proliferation rate of the BMSCs in OP model group was reduced, concentrations of bone formation markers (OC, PINP and BALP) were reduced, m RNA and protein expression levels of TGFβ, as well as the phosphorylated level of Smad2/3 were downregulated.The difference was statistically significant (P＜0.05). After treatment with OK, compared with model group, all the above effects were ameliorated in different degree, a dose dependent manner was observed in OK treatment group, and the treatment effects of alendronate sodium (1 μmol/L), 100 mL/L and 200 mL/L OK group were statistically significant (P ＜0.05).Conclusion OK can promote the proliferation of osteoblasts by activating TGFβ/Smad signaling pathway to achieve the effect of treating postmenopausal OP.
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Hepatic fibrosis is a damage and repair response model in chronic liver damage process.Hepatic stellate cells (HSC) play a determinant role as the main cells to produce liver extracellular matrix in the process of liver fibrosis,the activation and proliferation of HSC is the key link in liver fibrosis.Cholestasis is refers to the disorder in generation,secretion and flow of bile at the hepatocyte or bile duct level.The proteins exist in membranes of the liver cells and bile duct cells are important transporters to produce and secrete bile.In recent years,much progress have been made in signal transduction pathways of liver fibrosis,and the relevant research of cholestatic liver fibrosis is increasingly improvement,with the in-depth understanding of these transporters,complex signal network system of bile salt's synthesis and transport,this paper mainly through TGF-β/Smad,MAPK,JAK/STAT,NF-κ B and Wnt signal pathways to investigate the progress of signal transduction mechanism of cholestatic hepatic fibrosis.