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Terpenoids: The Biological Key Molecules
Published in Dijendra Nath Roy, Terpenoids Against Human Diseases, 2019
Moumita Majumdar, Dijendra Nath Roy
The transforming growth factor β (TGF-β) superfamily comprises numerous growth factors—including, for example, TGF-β-1,2,3 and bone morphogenetic proteins—by which they regulate physiological processes such as cell differentiation, development, proliferation, adhesion, movement and, ultimately, programmed cell death. Cytokines of the TGF-β superfamily accelerate heterotetrameric receptor complex formation. These structures are composed of mainly two transmembrane receptor proteins, namely TGF-β receptor I (TβRI) and TGF-β receptor II (TβRII). Phosphorylation of these receptors results in the activation of a downstream transcription factor, which in turn phosphorylates SMAD2 and SMAD3. TGF-β receptor 1 phosphorylates R-SMADs on their C terminus through the intracellular kinase domain, leading to R-SMAD activation (Wharton and Derynck 2009). Then, R-SMADs interact with SMAD4 to form a SMAD complex, leading to its translocation to the nucleus for gene expression. On the other hand, bone morphogenetic proteins activate SMADl, SMAD5 and SMAD8.
3D printing silk-gelatin-propanediol scaffold with enhanced osteogenesis properties through p-Smad1/5/8 activated Runx2 pathway
Published in Journal of Biomaterials Science, Polymer Edition, 2021
Caiyun Liu, Zhenzu Bai, Jiayu Lin, Kai Jiang, Shan Huang, Weijia Zheng, Ruifen Chen, Yang Xiang, Xiaoyan Wang, Long Liu
The phosphorylated Smad protein can transfer into the nucleus and play an important role as a transcription factor, activating the downstream target genes to regulate bone formation [26]. Erk is the key factor to transfer the signal from receptors to the nucleus. This signaling pathway regulates cell growth, differentiation and division. Phosphorylated Erk1/2 could mediate transcriptional activation of downstream target genes [27]. In this study, the results showed that the phosphorylation levels of Smad1/5/8 protein were significantly higher in MC3T3-E1 cells cultured on S-Gel-PG25 and S-Gel-PG30 scaffolds than the cells cultured on S-Gel-Gly25 and S-Gel-Ery25 scaffolds (Figure 5A and 5B), while there is no significant difference in p-Erk1/2 expression among MC3T3-E1 cells cultured on S-Gel-PG25 and S-Gel-PG30 scaffolds as well as the cells cultured on S-Gel-Gly25 scaffold (Figure 5C and 5D). Therefore, these data indicated that S-Gel-PG25 and S-Gel-PG30 scaffolds may enhance the proliferation, differentiation and mineralization of MC3T3-E1 cells through p-Smad1/5/8 pathway, but not p-Erk1/2 pathway.
Transcriptome analysis of Takifugu obscurus liver in response to acute retene exposure
Published in Journal of Environmental Science and Health, Part A, 2020
Shulun Jiang, Di-an Fang, Dongpo Xu
The SMAD family regulates intracellular events of the transforming growth factor β (TGFβ) signaling pathway, which controls cellular processes involving cell proliferation, differentiation, apoptosis, and tumorigenesis.[62] SMAD4 mediates TGF-beta activities and regulates the actions of all the R-SMADs.[63] SMAD4 is needed for gastrulation and acts to suppress gastric cancer in mice.[64] Moreover, SMAD3 also participates in tumorigenesis, immune response, and the skeleton development of mice.[64] Following retene exposure, unusual activation of the FOXO pathway may be attributed to an immune response or to cell repair. Moreover, overactivation of FOXO pathways may distrupt the normal cycle and result in an increased risk of tumorigenesis.