Transforming growth factor (TGF)-β is a group of cytokines with anti-inflammatory effects in the TGF family, which participates in the development of stress and depression-related mechanisms, and plays roles in the regulation of inflammatory response in depression and the recovery of various cytokine imbalances. The core symptoms of depression is associated with TGF-β level, and the psychological symptoms of depression are related to TGF-β gene polymorphism. Various antidepressants may up-regulate TGF-β level through the complex interaction between neurotransmitters and inflammatory factors, inhibiting inflammatory response and regulating cytokine imbalance to improve depressive symptoms. Studies have shown that recombinant TGF-β1 protein has beneficial effects in mouse depression models, indicating TGF-β1 might be a potential therapeutic target for depression and nasal sprays having the advantage of being fast acting delivery method. This article reviews the research progress on dynamic changes of TGF-β level before and after depression treatment and the application of TGF-β level as an indicator for the improvement of depressive symptoms. We provide ideas for the development of new antidepressants and for the evaluation of the treatment efficacy in depression.
Animals ; Mice ; Transforming Growth Factor beta/metabolism* ; Transforming Growth Factor beta1 ; Depression ; Cytokines ; Antidepressive Agents/therapeutic use* ; Transforming Growth Factors

The hallmark of scleroderma is fibrosis by excessive extracellular matrix (ECM) deposition in the skin, lung, and other organs. Increasing evidence suggests that overexpression of transforming growth factor-beta (TGF-beta) and its receptors play a key pathogenic role in the development of tissue fibrosis in scleroderma. TGF-beta is known to induce the expression of ECM proteins in the pathogenesis of fibrosis in systemic sclerosis. Investigations into TGF-beta pathways will suggest new treatment strategies for fibrotic diseases.
Animals ; Extracellular Matrix ; metabolism ; pathology ; Extracellular Matrix Proteins ; metabolism ; Fibroblasts ; metabolism ; Fibrosis ; Humans ; Receptors, Transforming Growth Factor beta ; metabolism ; Scleroderma, Systemic ; etiology ; metabolism ; Transforming Growth Factor beta ; metabolism

OBJECTIVETo explore the role of transforming growth factor beta (TGF beta) and their receptors (TGF beta-R) in the pathogenesis of hypertrophic scar.

METHODSSpecimens of normal skin and hypertrophic scar were harvested and the distribution and the expression of the TGF beta and TGF beta-R were determined by immunohistochemistry and in situ hybridization method.

RESULTSThe expressions of TGF beta and TGF beta-RII in normal skin were higher than the expression of TGF beta 1, TGF beta 2 and TGF-RI. But in hypertrophic scar the results were on the contrary. The mRNA expressions of TGF beta 1, TGF beta 2 and TGFRI were evidently increased with decreased mRNA expression of TGF-beta 3 and TGFR II in the hypertrophic scar when compared with those in the normal skin.

CONCLUSIONThe expression of TGF-beta (beta 1, beta 2, beta 3) and their receptors in different levels during the process of wound healing might be related to the formation of hypertrophic scars.

Cicatrix, Hypertrophic ; genetics ; metabolism ; Humans ; Immunohistochemistry ; In Situ Hybridization ; RNA, Messenger ; genetics ; metabolism ; Receptors, Transforming Growth Factor beta ; genetics ; metabolism ; Skin ; metabolism ; pathology ; Transforming Growth Factor beta ; genetics ; metabolism

OBJECTIVETo explore the possible effect of transforming growth factor-beta(1) (TGF -beta(1)) on the development of renal fibrosis in human mesengial proliferative glomerulonephritis (MsPGN).

METHODSImmunohistochemistry method, sirius red staining polarization microscopy and the computer imaging analysis system were used to detect the expression of TGF-beta(1), the distribution of collagen I, collagen III and collagen IV.

RESULTIn MsPGN with renal fibrosis, collagen IV was increased markedly,and collagen I and collagen III appeared in the expanded mesengial matrix abnormally. Collagen III and collagen IV were increased markedly in tubulointerstitium. TGF-beta(1) expression was positively correlated with the expression of collagen I, collagen III and collagen IV in tubulointerstitium (r=0.82 0.92,P<0.01), and negatively correlated with I/III, I/IV and III/IV (r=-0.83,-0.92, P<0.001).

CONCLUSIONAbnormal increase of TGF-beta(1) may be one of the important factors associated with glomerular sclerosis and tubulointerstitial fibrosis through the increment and abnormal distribution of collagen I, collagen III and collagen IV.

Collagen ; analysis ; Fibrosis ; Glomerulonephritis, Membranoproliferative ; metabolism ; pathology ; Humans ; Immunohistochemistry ; Kidney ; pathology ; Transforming Growth Factor beta ; analysis ; Transforming Growth Factor beta1

BACKGROUND: TGF - beta is known as a cell growth inhibitory factor to suppress almost all cells, including the epithelial cell. Unlike normal cells, cancer cells are not affected by TGF- beta growth inhibitory action and the lack of TGF- beta receptor expression or mutation is being reported as its mechanism, which is rarely studied in Korea. Therefore, we investigated this study to clarify the role of TGF - beta I and TGF - beta II receptors in gastric cancer. METHODS: 23 cases that underwent operations for gastric cancer provided RNA collected from their carcinoma tissues and adjacent normal tissues. We investigated the level of TGF - beta 1 and T beta R-II mRNA expression with semi- quantitatively reverse transcription PCR and analyzed the correlation with prognostic factors, such as tumor size, depth of invasion, tumor differentiation and lymph-node metastasis. RESULTS: (1) TGF- beta I and T beta R-II mRNA were expressed in all carcinoma tissues and adjacent normal tissues of the 23 cases without statistical difference in the level of the expression. (2) The level of TGF - beta 1 mRNA expression was higher in patients with gastric cancer invaded only at the mucosa and submucosa than in patients with gastric cancer invaded over muscular propria, and also higher in the patients without lymph-node metastasis or perineural invasion than in the patients with lymph-node metastasis or perineural invasion. There was no significant correlation between the level of T beta R-II mRNA expression and several parameters, such as age, gender, tumor size, location, differentiation, Lauren's classification and vascular invasion. (3) There was a significant correlation between the level of TGF - beta 1 and T beta R-II mRNA expression in carcinoma tissues. CONCLUSION: It indicated that TGF - beta 1 mRNA expression in gastric cancer might concern the early stage of gastric carcinogenesis and, unlike the earlier reports, it was higher in patients with early gastric cancer, negative lymph-nodes or negative perineural invasion. Further studies are required to clarify the role of TGF - beta 1 in gastric carcinogenesis with more patients.
Female ; Human ; Male ; Middle Age ; Prognosis ; RNA, Messenger/genetics/metabolism ; Receptors, Transforming Growth Factor beta/*genetics ; Stomach Neoplasms/*genetics/metabolism ; Transforming Growth Factor beta/metabolism

Although sympathetic blockade is clinically used to treat pain, the underlying mechanisms remain unclear. We developed a localized microsympathectomy (mSYMPX), by cutting the grey rami entering the spinal nerves near the rodent lumbar dorsal root ganglia (DRG). In a chemotherapy-induced peripheral neuropathy model, mSYMPX attenuated pain behaviors via DRG macrophages and the anti-inflammatory actions of transforming growth factor-β (TGF-β) and its receptor TGF-βR1. Here, we examined the role of TGF-β in sympathetic-mediated radiculopathy produced by local inflammation of the DRG (LID). Mice showed mechanical hypersensitivity and transcriptional and protein upregulation of TGF-β1 and TGF-βR1 three days after LID. Microsympathectomy prevented mechanical hypersensitivity and further upregulated Tgfb1 and Tgfbr1. Intrathecal delivery of TGF-β1 rapidly relieved the LID-induced mechanical hypersensitivity, and TGF-βR1 antagonists rapidly unmasked the mechanical hypersensitivity after LID+mSYMPX. In situ hybridization showed that Tgfb1 was largely expressed in DRG macrophages, and Tgfbr1 in neurons. We suggest that TGF-β signaling is a general underlying mechanism of local sympathetic blockade.
Mice ; Animals ; Receptor, Transforming Growth Factor-beta Type I/metabolism* ; Transforming Growth Factor beta/pharmacology* ; Transforming Growth Factor beta1/metabolism* ; Hyperalgesia/metabolism* ; Radiculopathy/metabolism* ; Pain/metabolism* ; Analgesics/pharmacology* ; Ganglia, Spinal/metabolism*

Tumorigenesis and cancer progression are closely associated with the transforming growth factor-beta (TGF-beta) and its downstream component Smad. The TGF-beta/Smad signaling pathway, which is activated in prostate cancer, has a regulatory effect on cell adhesion, the actin filament system and cell cycle, as well as the expression of specific genes. Meanwhile, other protein signals such as MAPK and PI3K/Akt/mTOR and some genes may act on the expression of the TGF-beta/Smad pathway. This article updates recent researches on the expression, action and regulatory effect of the TGF-beta/Smad signaling pathway in prostate cancer.
Humans ; Male ; Prostatic Neoplasms ; metabolism ; Signal Transduction ; Smad Proteins ; metabolism ; Transforming Growth Factor beta ; metabolism

As a crucial regulatory molecule in the context of vascular stenosis, transforming growth factor-β (TGF-β), plays a pivotal role in its initiation and progression. TGF-β, a member of the TGF-β superfamily, can bind to the TGF-β receptor and transduce extracellular to intracellular signals through canonical Smad dependent or noncanonical signaling pathways to regulate cell growth, proliferation, differentiation, and apoptosis. Restenosis remains one of the most challenging problems in cardiac, cerebral, and peripheral vascular disease worldwide. The mechanisms for occurrence and development of restenosis are diverse and complex. The TGF-β pathway exhibits diversity across various cell types. Hence, clarifying the specific roles of TGF-β within different cell types and its precise impact on vascular stenosis provides strategies for future research in the field of stenosis.
Humans ; Transforming Growth Factor beta/metabolism* ; Constriction, Pathologic ; Signal Transduction ; Cell Differentiation ; Vascular Diseases ; Transforming Growth Factors ; Transforming Growth Factor beta1

OBJECTIVETo investigate the antitumor effect of natural killer (NK) cells on human colorectal cancer cells HT-29 in vitro by blocking transforming growth factor-&beta; (TGF-&beta;) signaling in NK cells transfected with vector containing dominant negative TGF-&beta; type 2 receptor (DNT&beta;R2).

METHODSTGF-&beta;1 was added at the final concentration of 10 ng/ml for HT-29 cells. Primary NK cells were transfected with recombinant plasmid pIRES2-AcGFP-DNT&beta;R2 and control plasmid pIRES2-AcGFP using Amaxa Nucleofector technology respectively. The cytotoxicity of these two types of NK cells to HT-29 cells was detected and analyzed by cell counting kit-8.

RESULTSThe transfection efficiency of primary NK cells was 18.85% for the plasmid pIRES2-AcGFP-DNT&beta;R2 and 35.28% for the control plasmid pIRES2-AcGFP. The expression of DNT&beta;R2 in NK cells was confirmed by Western blotting and RT-PCR. Primary NK cells displayed significantly lower cytotoxicity against HT-29 cells incubated with TGF-&beta;1 than that without TGF-&beta;1 (effect-target cell ratio 10:1,14.40%∓ 2.00% vs. 26.14% ∓ 2.50%, P > 0.05; effect-target cell ratio 20:1, 19.18% ∓ 2.49% vs. 40.81% ∓ 3.50%, P > 0.05). The cytotoxicity of NK cells transfected with DNT&beta;R2 vector was significantly higher than that with control vector against HT-29 cells cultured with 10 ng/ml TGF-&beta;1 (effect-target cell ratio 10:1, 21.17% ∓ 2.49% vs. 11.48% ∓ 1.11% ,P > 0.05; and effect-target cell ratio 20:1, 35.30% ∓ 3.78% vs. 17.19% ∓ 2.29%, P > 0.05).

CONCLUSIONNK cells transfected with DNT&beta;R2 vector show better antitumor effect, which may provide new method for NK-based adoptive immunotherapy for cancer.

HT29 Cells ; Humans ; Killer Cells, Natural ; immunology ; metabolism ; Plasmids ; genetics ; Receptors, Transforming Growth Factor beta ; genetics ; Transfection ; Transforming Growth Factor beta ; metabolism ; pharmacology

Transforming growth factor-β (TGF-β) members are key cytokines that control embryogenesis and tissue homeostasis via transmembrane TGF-β type II (TβR II) and type I (TβRI) and serine/threonine kinases receptors. Aberrant activation of TGF-β signaling leads to diseases, including cancer. In advanced cancer, the TGF-β/SMAD pathway can act as an oncogenic factor driving tumor cell invasion and metastasis, and thus is considered to be a therapeutic target. The activity of TGF-β/SMAD pathway is known to be regulated by ubiquitination at multiple levels. As ubiquitination is reversible, emerging studies have uncovered key roles for ubiquitin-removals on TGF-β signaling components by deubiquitinating enzymes (DUBs). In this paper, we summarize the latest findings on the DUBs that control the activity of the TGF-β signaling pathway. The regulatory roles of these DUBs as a driving force for cancer progression as well as their underlying working mechanisms are also discussed.
Animals ; Humans ; Molecular Targeted Therapy ; Receptors, Transforming Growth Factor beta ; metabolism ; Signal Transduction ; Smad Proteins ; physiology ; Transforming Growth Factor beta ; physiology ; Ubiquitin Thiolesterase ; metabolism ; Ubiquitin-Specific Proteases ; Ubiquitination