TGF-β Fibrosis Pathway Antibody Sampler Kit #77397
Product Information
Kit Usage Information
Protocols
- 3709: Western Blotting
- 5339: Western Blotting, Immunoprecipitation (Agarose), Immunofluorescence, Flow, ChIP Magnetic
- 7074: Western Blotting
- 8685: Western Blotting, Immunoprecipitation (Agarose), Immunofluorescence, Flow, ChIP Magnetic, Chromatin IP-seq
- 8828: Western Blotting
- 18338: Western Blotting, Immunoprecipitation (Agarose), Immunofluorescence, Flow, ChIP Magnetic
- 19245: Western Blotting, Immunoprecipitation (Magnetic), Immunohistochemistry (Leica® Bond™), Immunohistochemistry (Paraffin), Immunofluorescence
- 41896: Western Blotting
- 47066: Western Blotting, Immunohistochemistry (Paraffin), Immunofluorescence
- 91144: Western Blotting, Immunoprecipitation (Magnetic)
Product Description
Specificity / Sensitivity
Source / Purification
Background
TGF-β elicits signaling through three cell surface receptors: type I (RI), type II (RII), and type III (RIII). In response to ligand binding, the type II receptors form stable heterotrimeric complexes with the type I receptors, allowing phosphorylation and activation of type I receptor kinase. Activated type I receptors associate with SMAD2/3 and phosphorylate them on a conserved carboxy terminal SSXS motif. The phosphorylated SMADs dissociate from the receptor and form a heterotrimeric complex with the co-Smad (Smad4), allowing translocation of the complex to the nucleus. Once in the nucleus, phosphorylated SMAD2/3 targets a subset of DNA binding proteins to regulate the transcriptional program (6-8).
In the context of fibrosis, SMAD2/3 activation upregulates expression of profibrotic genes such as COL1A1 and other ECM modulators that modify the extracellular matrix of the tissue. (9). TGF-β/ SMAD2/3 signaling also induces expression of α-Smooth Muscle Actin in fibroblasts, causing transformation of these cells to myofibroblasts (10). Myofibroblasts further modify the ECM, causing excessive accumulation of collagens and other ECM components. Injury to the tissue attracts macrophages and other immune cells and the fibrotic tissue soon becomes a site of inflammation (11). In this pro-fibrotic, pro-inflammatory environment, YKL-40, also known as Chitinase-3-like protein 1 (CHI3L1), is secreted. YKL-40 is a pro-inflammatory glycoprotein that also contributes to the progression of fibrosis (12). Measurement of collagen content, α-Smooth Muscle Actin, and the release of YKL-40 are predictive of fibrotic activity.
- Massagué, J. et al. (2000) Cell 103, 295-309.
- de Caestecker, M.P. et al. (2000) J Natl Cancer Inst 92, 1388-402.
- Derynck, R. et al. (2001) Nat Genet 29, 117-29.
- Miyazono, K. et al. (2000) Adv Immunol 75, 115-57.
- Meng, X.M. et al. (2016) Nat Rev Nephrol 12, 325-38.
- Wu, G. et al. (2000) Science 287, 92-7.
- Attisano, L. and Wrana, J.L. (2002) Science 296, 1646-7.
- Moustakas, A. et al. (2001) J Cell Sci 114, 4359-69.
- Bagalad, B.S. et al. J Oral Maxillofac Pathol 21, 462-3.
- Mack, M. (2018) Matrix Biol 68-69, 106-21.
- Johansen, J.S. (2006) Dan Med Bull 53, 172-209.
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