Transforming growth factor β (TGF-β) is a group of structurally similar transforming growth factors that have multiple functions to regulate cell functions, such as regulating cell proliferation and differentiation, apoptosis, cell migration, and cell adhesion. In addition, they play important roles in embryonic development, immune monitoring, and stem cell self-renewal and differentiation. Furthermore, TGF-β plays an important role in maintaining the normal structure of the vascular wall and has a certain protective effect on atherosclerosis. In endothelial cells, TGF-β inhibits the activation of endothelial cells and reduces the recruitment of lymphocytes by inhibiting the expression of the adhesion factor E-selectin. The proliferation of vascular smooth muscle cells can be inhibited by TGF-β, which promote collagen formation, and proliferate extracellular matrix. Besides, TGF-β can affect the uptake of fat particles by macrophages, thereby reducing the formation of foam cells.

Mechanism and Function

There are five isomers of the TGF-β superfamily: TGF-β1, TGF-β2, TGF-β3, TGF-β4, and TGF-β5, which are dimeric structures consisting of 9 highly conserved cysteine residues connected by disulfide bonds. TGF-β has a wide range of biological functions in vivo and in vitro, including regulating cell growth, regulating cell phenotype, and inhibiting tumor growth. TGF-β receptors are widely expressed in tissue cells of the body, and most normal cells in the body express membrane-bound receptors of members of the TGF-β family. Since TGF-β has a highly specific affinity for its receptors, TGF-β exerts a regulatory effect on many cells. Growth inhibition is a unique property of TGF-β, it has an inhibitory effect on the proliferation of most cells, especially epithelial cells, endothelial cells, lymphoid cells and hematopoietic cells. The function expressed by TGF-β is related to the cell type. TGF-β3 plays an important role in normal wound healing in the lung, while TGF-β1 plays an important role in fibrotic wound healing in the lung. In addition, TGF-β2 mediates epithelial-mesenchymalization of the heart pad by promoting the initiation and cessation of epithelial-to-mesenchymal transition. In the nervous system, TGF-β1 has a neuroprotective effect.

The TGF-β family transmits signals mainly through Smad family proteins. According to different functions, Smad proteins are divided into 3 categories. The first category is receptor regulated Smad (R-Smad), including Smad1, Smad2, Smad3, Smad5, and Smad8; the second category is co-mediator Smad (Co-Smad), including Smad4; the third category is inhibitory Smad (I-Smad), including Smad6 and Smad7. TGF-β participates in regulating cell function by binding to TGF-β receptors on the cell surface. TGF-β binds to cell surface TGF-β receptors to phosphorylate the receptor. The phosphorylated receptor recruits and phosphorylates the downstream molecule R-Smads. In this process, the helper protein SARA is required to make R-Smad easily bind to the phosphorylated receptor. When the SSXS motif at the C-terminus of the R-Smad protein is phosphorylated, it is dissociated from the receptor complex, forms a heterodimer complex with Co-Smad. The complex is transferred into the nucleus, and regulates the target gene with transcription factors. I-Smad mainly inhibits activation of this signaling pathway by competing with R-Smad for binding to activated receptors and ubiquitinating them, degrading activated receptors, or dephosphorylation through other pathways.

Mechanism of Signaling  Fig 1. Mechanism of Signaling

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We mainly provide the Luminex cytokine detection platform. Luminex uses fluorescently encoded microspheres with specific antibodies to different target molecules. The different microspheres can be combined freely to a certain extent so that up to 100 analytes can be tested multiple times simultaneously in a single experiment.

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  1. Shi Y, Massague J. Mechanisms of TGF-beta sinaling from cell membrane to the nucleus. Cell, 2003, 113(6):685-700.
  2. Ungefroren H, Groth S, Sebens S, et al. Differential roles of Smad2 and Smad3 in the regulation of TGF-β1-mediated growth inhibition and cell migration in pancreatic ductal adenocarcinoma cells: control by Rac1. Mol Cancer, 2011,10(1):67.
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