TGFB1是一種細(xì)胞因子，可影響細(xì)胞增殖、分化、凋亡和胚胎發(fā)育等生物學(xué)過程。最近的研究表明，TGFB1在心臟疾病和纖維化方面發(fā)揮著重要作用。例如，一項研究發(fā)現(xiàn)，通過阻斷TGFB1信號通路可以減輕心肌缺血再灌注損傷引起的心肌纖維化。此外，TGFB1在腫瘤發(fā)生和發(fā)展中也發(fā)揮著重要作用，其過度表達(dá)與癌細(xì)胞增殖、轉(zhuǎn)移和免疫逃逸相關(guān)。

Transforming growth factor beta-1 proprotein: Precursor of the Latency-associated peptide (LAP) and Transforming growth factor beta-1 (TGF-beta-1) chains, which constitute the regulatory and active subunit of TGF-beta-1, respectively.; Required to maintain the Transforming growth factor beta-1 (TGF-beta-1) chain in a latent state during storage in extracellular matrix. Associates non-covalently with TGF-beta-1 and regulates its activation via interaction with 'milieu molecules', such as LTBP1, LRRC32/GARP and LRRC33/NRROS, that control activation of TGF-beta-1. Interaction with LRRC33/NRROS regulates activation of TGF-beta-1 in macrophages and microglia (Probable). Interaction with LRRC32/GARP controls activation of TGF-beta-1 on the surface of activated regulatory T-cells (Tregs). Interaction with integrins (ITGAV:ITGB6 or ITGAV:ITGB8) results in distortion of the Latency-associated peptide chain and subsequent release of the active TGF-beta-1.; Multifunctional protein that regulates the growth and differentiation of various cell types and is involved in various processes, such as normal development, immune function, microglia function and responses to neurodegeneration. Activation into mature form follows different steps: following cleavage of the proprotein in the Golgi apparatus, Latency-associated peptide (LAP) and Transforming growth factor beta-1 (TGF-beta-1) chains remain non-covalently linked rendering TGF-beta-1 inactive during storage in extracellular matrix. At the same time, LAP chain interacts with 'milieu molecules', such as LTBP1, LRRC32/GARP and LRRC33/NRROS that control activation of TGF-beta-1 and maintain it in a latent state during storage in extracellular milieus. TGF-beta-1 is released from LAP by integrins (ITGAV:ITGB6 or ITGAV:ITGB8): integrin-binding to LAP stabilizes an alternative conformation of the LAP bowtie tail and results in distortion of the LAP chain and subsequent release of the active TGF-beta-1. Once activated following release of LAP, TGF-beta-1 acts by binding to TGF-beta receptors (TGFBR1 and TGFBR2), which transduce signal. While expressed by many cells types, TGF-beta-1 only has a very localized range of action within cell environment thanks to fine regulation of its activation by Latency-associated peptide chain (LAP) and 'milieu molecules'. Plays an important role in bone remodeling: acts as a potent stimulator of osteoblastic bone formation, causing chemotaxis, proliferation and differentiation in committed osteoblasts. Can promote either T-helper 17 cells (Th17) or regulatory T-cells (Treg) lineage differentiation in a concentration-dependent manner. At high concentrations, leads to FOXP3-mediated suppression of RORC and down-regulation of IL-17 expression, favoring Treg cell development. At low concentrations in concert with IL-6 and IL-21, leads to expression of the IL-17 and IL-23 receptors, favoring differentiation to Th17 cells. Stimulates sustained production of collagen through the activation of CREB3L1 by regulated intramembrane proteolysis (RIP). Mediates SMAD2/3 activation by inducing its phosphorylation and subsequent translocation to the nucleus. Can induce epithelial-to-mesenchymal transition (EMT) and cell migration in various cell types.

1. CTEN activated the expression of TGFB1, thereby prompting epithelial-mesenchymal transition in lung adenocarcinoma cancer cells. PMID: 29985912
2. blocking TGF-b signaling with the TGF-b receptor inhibitor SB431542 counteracted the effect of platelets on KLF6 expression and proliferation of HCC cells. Based on these findings, we conclude that platelet releasates, especially TGF-b, promote the proliferation of SMMC.7721 and HepG2 cells by decreasing expression of KLF6 PMID: 28638139
3. Stimulation of cancer cells with TGFbeta1 weakened the ability of glioblastoma cells to attract hematopoietic stem cells (HSCs) and exchange a fluorescent tag. This process stimulated cancer cell proliferation, which is an indication of the ability of HSCs to 'switch' the proliferation and invasion processes in glioblastoma cells. PMID: 30226551
4. Long non-coding RNA 886 is induced by TGF-beta and suppresses the microRNA pathway in ovarian cancer. PMID: 29563500
5. these findings demonstrate that JunB and CBP-mediated histone hyperacetylation are responsible for TGF-beta1 induced ITGB6 transcription in oral squamous cell carcinoma (OSCC) cells, suggesting that epigenetic mechanisms are responsible for the active transcription expression of ITGB6 induced by TGF-beta1 in OSCC cells. PMID: 29274289
6. TGF-beta induces MIR100HG lncRNA, encoding miR-100, let-7a and miR-125b that control pancreatic ductal adenocarcinoma tumorigenesis. Pro-tumorigenic miR-100 and miR-125b increase and anti-tumorigenic let-7a is unchanged, as TGF-beta also induces LIN28B. The induction of LIN28B results in the up-regulation of miR-100 and miR-125b, with let-7a unchanged despite being part of the same MIR100HG primary transcript. PMID: 29748571
7. expression increased in cervical intraepithelial neoplasia (CIN) I and CIN II and decreased in CIN III and cancer PMID: 30059872
8. Studies indicate that transforming growth factor-beta (TGF-beta) has an important role in tissue fibrosis by up-regulating matrix protein synthesis, inhibiting matrix degradation, and altering cell-cell interaction [Review]. PMID: 30150520
9. A possible mechanism has been proposed of the TGF-beta-VEGF-C pathway in which TGF-beta promotes VEGF-C production in tubular epithelial cells, macrophages, and mesothelial cells, leading to lymphangiogenesis in renal and peritoneal fibrosis. (Review) PMID: 30142879
10. we observed that human TGF-beta1 could up-regulate the expression of CD147 in response to arecoline and that inhibition of TGF-beta1 could down-regulate this expression. The data presented here suggest that TGF-beta1 may promote OSF progression via CD147. PMID: 29457855
11. TGF-beta activity is elevated in human heterotopic ossification patients. PMID: 29416028
12. FZD8 silencing reduces prostate cancer cell migration, invasion, three-dimensional (3D) organotypic cell growth, expression of EMT-related genes, and TGF-beta/Smad-dependent signaling PMID: 29717114
13. Data suggest that resolvin D1/RVDR1 signaling (1) promotes epithelial wound repair, (2) inhibits TGFB-induced epithelial-mesenchymal transition in type II alveolar cells, (3) inhibits fibroproliferation and apoptosis, (4) reduces effects of TGFB on primary lung fibroblast collagen production, and (5) inhibits myofibroblast differentiation. (RVDR1 = resolvin D1 receptor) PMID: 29083412
14. this paper shows that TGF-beta1 alters esophageal epithelial barrier function by attenuation of claudin-7 in eosinophilic esophagitis PMID: 28832026
15. on the basis of present results, TGFB1 (-509C/T) can be considered as a predisposing factor of idiopathic scoliosis (IS)with a moderate individual effect on deformity development in Bulgarian patients; results may suggest that there is an association of the TGFB1 (-509C/T) polymorphism with susceptibility to IS in the female population with sporadic or familial IS and early or late onset IS PMID: 30079294
16. Treatment of GLS1-deficient myofibroblasts with exogenous glutamate or alpha-KG restored TGF-beta1-induced expression of profibrotic markers in GLS1-deficient myofibroblasts. Together, these data demonstrate that glutaminolysis is a critical component of myofibroblast metabolic reprogramming that regulates myofibroblast differentiation. PMID: 29222329
17. High TGFB1 expression is associated with cardiac fibrosis. PMID: 30340644
18. Our findings provide a novel insight of endometriosis that the hypoxic microenvironment stimulates endometrial stromal cells to produce excessive TGF-beta1 and activates the TGF-beta1/Smad signaling pathway, thus enhancing integrin expression and the adhesion ability of endometrial stromal cells. PMID: 29438550
19. Prodomain-growth factor swapping in the structure of pro-TGF-beta1. PMID: 29109152
20. Inductive effect of TGF-beta on podoplanin seems to be limited. PMID: 29577431
21. RHCG was down-regulated in cervical cancers compared to that in normal cervical tissues, and further decreased in cervical cancer cell lines. Functionally, RHCG overexpression reduced cervical cancer cell proliferation and migration, as evidenced by the decreased transforming growth factor (TGF)-beta1, matrix metalloproteinase (MMP)-2 and MMP-9 expressions in cancer cells. PMID: 29852177
22. Following Schistosoma exposure, TSP-1 levels in the lung increase, via recruitment of circulating monocytes, while TSP-1 inhibition or knockout bone marrow prevents TGF-beta activation and protects against pulmonary hypertension development. PMID: 28555642
23. TGFbeta1 reduced complex IV protein MTCO1 abundance in both myoblasts and myotubes. PMID: 29335583
24. TGF-beta1 expression is regulated by PlncRNA-1 in breast cancer. PMID: 29626321
25. Elevated AhR expression may be involved in the progression of tissue remodeling in chronic rhinosinusitis without nasal polyp without allergic rhinitis similar to TGF-beta1 expression PMID: 29183012
26. Overall, these findings suggest a more dominant role for SMAD3 and SMAD4 than SMAD2 in TGFbeta-induced chondrogenesis of human bone marrow-derived mesenchymal stem cells. PMID: 28240243
27. High TGF beta expression is associated with Chronic Periodontitis. PMID: 30051674
28. Fewer TIMP-2, Hsp70 and TGF-beta1 immunoreactive cells in younger individuals and increased expression of Hsp70 in elderly individuals demonstrated the influence of aging in lung remodeling PMID: 29325453
29. Data show that TGFbeta1-mediated EMT involves CD44 splice isoform switching in ovarian cancer cells. PMID: 29130517
30. Gene silencing experiments of MLL4 and the subunits PA1 and PTIP confirm TGF-beta-specific genes to be regulated by the MLL4 complex, which links TGF-beta signaling to transcription regulation by the MLL4 methyltransferase complex. PMID: 28976802
31. TGF-beta1 is significantly overexpressed in tumor tissue samples of clear cell Renal cell carcinoma patients. TGF-beta1 up-regulation could be responsible for the high levels of NNMT observed in clear cell Renal cell carcinoma tissues. PMID: 29974846
32. TGF-beta role in the promotion of DNA damage and genomic instability in cancer cells. PMID: 29074538
33. TGFbeta1 induced the expression alphaSMA, Col1 and fibronectin, and stimulated fibroblastmediated contraction of collagen gel. PMID: 30015862
34. miR-203 expression also inhibited primary tumor growth in ovaries and metastatic tumors in multiple peritoneal organs including liver and spleen. miR-203 inhibits ovarian tumor metastasis by targeting BIRC5/survivin and attenuating the TGFbeta pathway. PMID: 30241553
35. NK cells from liver cirrhosis (LC) patients could enter hepatic stellate to form emperipolesis (a cell-in-cell structure) and become apoptotic; anti-TGF-b treatment ameliorated this emperipolesis. PMID: 28291251
36. therapeutic activation of ERbeta elicits potent anticancer effects in Triple-negative breast cancer through the induction of a family of secreted proteins known as the cystatins, which function to inhibit canonical TGFbeta signaling and suppress metastatic phenotypes both in vitro and in vivo. PMID: 30257941
37. These findings suggest that TGFbeta plays a vital role in triple-negative breast cancer epirubicin-resistance through regulating stemness, Epithelial-Mesenchymal Transition and apoptosis. PMID: 29792857
38. TGF-beta release from platelets is necessary for podoplanin-mediated tumor invasion and metastasis in lung cancer. PMID: 28176852
39. Treating HepG2 cells with hepatotoxicants resulted in a significant increase in mRNA expression of platelet-derived growth factor BB (PDGF-BB) and transforming growth factor beta (TGFbeta). PMID: 29558627
40. In contrast with some reports involving the correlation between polymorphisms of the TGF-beta1 and IL-2 genes and inhibitor development in the world, no statistically significant differences in analysis of the alleles and genotypes for TGF-beta and IL-2 genes were found between the inhibitor and non-inhibitor Iranian patients PMID: 29993342
41. The findings of the present study indicated that miR326 inhibited endometrial fibrosis by suppressing the TGFbeta1/Smad3 signaling pathway, suggesting that miR326 may be a prognostic biomarker and therapeutic target for Intrauterine adhesion (IUA). PMID: 29956752
42. Characterization of gene expression profiles in hepatitis B-related liver fibrosis patients identified ITGBL1 and its interactions with TGFB1 as key regulators of fibrogenesis. PMID: 28262670
43. TGF-beta1 and arginase-1 may play important roles in determining long-term graft survival. PMID: 30074212
44. Two polymorphic sites of TGF-beta1 gene were identified: -509C/T and +869T/C. We found that the -509C/T polymorphism was associated with increased asthma risk under the heterozygous mode land the dominant model. Subgroup analyses by age suggested that -509C/T variant was associated with childhood asthma. PMID: 29958018
45. proinflammatory cytokines suppressed the TGFbetamediated expression of NGF in PDLderived fibroblasts through the inactivation of TGFbetainduced Smad2/3 and p38 MAPK signaling. PMID: 29901090
46. FXR agonist treatment enhanced TGF-beta-induced epithelial mesenchymal transition(EMT) morphologic changes and FXR antagonist inhibited the effect of TGF-beta;. Thus, FXR activation enhances EMT in hepatocellular carcinoma (HCC) and FXR antagonists may be EMT-suppressing drug candidates. PMID: 29958417
47. Autosomal Dominant Polycystic Kidney Disease patients with moderately preserved renal function have higher levels of FasL, myostatin and urine TGF-beta1 than controls PMID: 29794429
48. No increased risk for developing immune thrombocytopenia (ITP) was associated with any allele/genotype of tumor necrosis factor beta (TNFB) + 252G/A gene polymorphism. PMID: 29020887
49. Suppression of TGF-beta1 enhances chemosensitivity of cisplatin-resistant lung cancer cells through the inhibition of drug-resistant proteins PMID: 28918673
50. The results of the present study indicated that CD8+ T cells with high TGFbeta1 expression served an important role in LN fibrosis following HIV infection. PMID: 29749506

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Camurati-Engelmann disease (CAEND)

[Latency-associated peptide]: Secreted, extracellular space, extracellular matrix.; [Transforming growth factor beta-1]: Secreted.

TGF-beta family

Highly expressed in bone. Abundantly expressed in articular cartilage and chondrocytes and is increased in osteoarthritis (OA). Colocalizes with ASPN in chondrocytes within OA lesions of articular cartilage.

HGNC: 11766

OMIM: 131300

KEGG: hsa:7040

STRING: 9606.ENSP00000221930

UniGene: Hs.645227