TGF-β receptors: In and beyond TGF-β signaling

Ark, Alexandra Vander; Cao, Jingchen; Li, Xiaohong

doi:10.1016/j.cellsig.2018.09.002

Cited by 356 publications

(268 citation statements)

References 113 publications

Supporting

Mentioning

252

Contrasting

Unclassified

Order By: Relevance

“…5c]. It is known that signaling starts with TGF-β binding to TGF-β receptor II and phosphorylates TGF-β receptor I resulting in phosphorylating downstream including Smad2 and 3 26 . Therefore, TGF-β receptor II expression level was examined.…”

Section: Gal-3 Production Caused By Pg-infection and -Lps Stimulatimentioning

confidence: 99%

Odontogenic infection by Porphyromonas gingivalis exacerbates fibrosis in NASH via hepatic stellate cell activation

Nagasaki

Sakamoto

Chea

et al. 2020

Sci Rep

View full text Add to dashboard Cite

odontogenic infection of Porphyromonas gingivalis (P.g.), a major periodontal pathogen, exacerbates pathological progression of non-alcoholic steatohepatitis (NASH). In this study, we aimed to clarify the detailed mechanism in which P.g. induced hepatic stellate cells (HSCs; key effector cells in liver fibrosis) activation. In the liver of high fat diet-induced NASH mouse model with P.g. odontogenic infection, immunolocalization of P.g. was detected. The number of hepatic crown-like structure, which was macrophage aggregation and related to liver fibrosis, was drastically increased and fibrosis area was also increased through upregulating immunoexpression of Phosphorylated Smad2 (key signaling molecule of TGF-β1) and Galectin-3. P.g.-secreted trypsin-like enzyme [gingipain; an activator of protease-activated receptor 2 (PAR2)] stimulated HSC proliferation and differentiation through Smad and ERK signaling induced by TGF-β1 produced from HSCs with P.g.-infection. Further, Galectin-3 produced from HSCs with P.g. infection and P.g.-derived LPS/lipoprotein stimulation stabilized TGFβ-receptor II resulting in increasing sensitivity for TGF-β1, finally leading to HSC differentiation via activating Smad and ERK signaling. In addition to them, hepatocytes (main component cells of liver) contributed to HSC activation through TGF-β1 and Galectin-3 production in paracrine manner. Collectively, P.g.-odontogenic infection exacerbates fibrosis of NASH by HSC activation through TGF-β1 and Gal-3 production from HSCs and hepatocytes.Non-alcoholic fatty liver disease (NAFLD) is a chronic hepatic disease caused by obesity including simple steatosis and non-alcoholic steatohepatitis (NASH). The morbidity rate of NAFLD is high, up to 30% in Western countries, with increasing the number of NAFLD patients because of the increase of obesity 1-3 . Most NAFLD patients indicate simple steatosis, which is a reversible condition, but 10-20% of simple steatosis progresses to NASH, which is presented as inflammation with hepatocyte degeneration followed by hepatic fibrosis 3 . As some of the NASH cases eventually result in liver cirrhosis and cancer, it is a critical health problem requiring adequate prevention and early therapeutic intervention 2,4 . The mechanisms for the development and progression of NASH are extremely complicated. Recently, it was reported that fat deposition, inflammation and fibrosis in NASH are simultaneously caused by many factors such as up-regulation of free fatty acids (FFA), oxidation stress, cytokines and bacterial lipopolysaccharide (LPS) 5 .Porphyromonas gingivalis (P.g.) is a main periodontal pathogen. Periodontitis caused by P.g. is a well-recognized risk factor for many systemic diseases such as cardiovascular disease, preterm birth, diabetes mellitus, and rheumatoid arthritis 6-9 . P.g. can enter the blood circulation from periodontal disease sites and disseminate into the whole body and it can be detected in the distant organs including liver 6,7,10,11 . Furusho et al. reported that P.g.-odontogenic infect...

show abstract

Section: Gal-3 Production Caused By Pg-infection and -Lps Stimulatimentioning

confidence: 99%

Odontogenic infection by Porphyromonas gingivalis exacerbates fibrosis in NASH via hepatic stellate cell activation

Nagasaki

Sakamoto

Chea

et al. 2020

Sci Rep

View full text Add to dashboard Cite

show abstract

“…Transforming growth factor β (TGFβ) plays a pivotal role during lung development and angiogenesis through the regulation of endothelial cell (EC) growth, differentiation, migration, senescence, and extracellular matrix (ECM) production [15][16][17][18][19] . TGFβ-mediated signalling is initiated by binding to a TGFβ specific membrane receptor complex in ECs that contains 3 types of receptors: type I and type II serine/threonine kinase receptors and a co-receptor or TGFβ type III receptor named endoglin, also known as CD105.…”

mentioning

confidence: 99%

S-endoglin expression is induced in hyperoxia and contributes to altered pulmonary angiogenesis in bronchopulmonary dysplasia development

Lee

Nam

et al. 2020

Sci Rep

View full text Add to dashboard Cite

Altered pulmonary angiogenesis contributes to disrupted alveolarization, which is the main characteristic of bronchopulmonary dysplasia (BPD). Transforming growth factor β (tGfβ) plays an important role during lung vascular development, and recent studies have demonstrated that endoglin is engaged in the modulation of tGfβ downstream signalling. Although there are two different isoforms of endoglin, L-and S-endoglin, little is known about the effect of S-endoglin in developing lungs. We analysed the expression of both L-and S-endoglin in the lung vasculature and its contribution to tGfβ-activin-like kinase (ALK)-Smad signalling with respect to BPD development. Hyperoxia impaired pulmonary angiogenesis accompanied by alveolar simplification in neonatal mouse lungs. S-endoglin, phosphorylated Smad2/3 and connective tissue growth factor levels were significantly increased in hyperoxia-exposed mice, while L-endoglin, phosphor-Smad1/5 and platelet-endothelial cell adhesion molecule-1 levels were significantly decreased. Hyperoxia suppressed the tubular growth of human pulmonary microvascular endothelial cells (ECs), and the selective inhibition of ALK5 signalling restored tubular growth. These results indicate that hyperoxia alters the balance in two isoforms of endoglin towards increased S-endoglin and that S-endoglin attenuates TGFβ-ALK1-Smad1/5 signalling but stimulates tGfβ-ALK5-Smad2/3 signalling in pulmonary ECs, which may lead to impaired pulmonary angiogenesis in developing lungs. open Scientific RepoRtS | (2020) 10:3043 | https://doi.org/10.1038/s41598-020-59928-x www.nature.com/scientificreports www.nature.com/scientificreports/ through enhancement of the TGFβ-ALK1-Smad1/5 pathway, while connective tissue growth factor (CTGF) expression increases through enhancement of the TGFβ-ALK5-Smad2/3 pathway [27][28][29][30][31] .Several independent findings have demonstrated that endoglin is engaged in TGFβ receptor complex formation and the modulation of downstream signalling [32][33][34][35] . The expression of two alternatively spliced isoforms, long (L-) endoglin and short (S-) endoglin, has been demonstrated in human and mouse lung tissues in vivo 33,34,36,37 . L-endoglin is the predominant isoform, and its pre-mRNA can be alternatively spliced by intron retention, producing the less abundant form, S-endoglin 36,37 . Evidence indicates that L-endoglin, the predominant isoform in ECs, promotes EC proliferation via TGFβ-ALK1 signalling, whereas S-endoglin acts as an antagonist of L-endoglin via activation of the TGFβ-ALK5 pathway 32,33,36,37 .To date, most studies published on endoglin have focused on L-endoglin. It has been found that L-endoglin enhances ALK1-Smad1/5 signalling in ECs, leading to proliferation and migration, which are the main characteristics of the activation phase of angiogenesis 15,18,20,22,[38][39][40][41][42][43] . However, a role of S-endoglin during endothelial senescence was recently described 36,37 . The S-endoglin:L-endoglin ratio increases during the senescence of ECs in vitro as well ...

show abstract

“…25,26 TGFBR1, one of the receptor ligand of TGF-β, transduces the TGF-beta signaling through phosphorylating SMAD2/3 or no canonical downstream components. 27 In our study, we demonstrated that miR-27a might directly target TGFBR1 3′UTR. In addition, TGFBR1 overexpression rescues effects of miR-27a inhibitor on DLBCL cells phenotypes.…”

Section: Discussionmentioning

confidence: 50%

“…In malignant B lymphocytes, TGF‐β signaling had been reported as a tumor suppressor . TGFBR1, one of the receptor ligand of TGF‐β, transduces the TGF‐beta signaling through phosphorylating SMAD2/3 or no canonical downstream components . In our study, we demonstrated that miR‐27a might directly target TGFBR1 3′UTR.…”

Section: Discussionmentioning

confidence: 52%

Pre‐miR‐27a rs895819 polymorphism and risk of diffuse large B‐cell lymphoma

Tang

et al. 2019

Clinical Laboratory Analysis

View full text Add to dashboard Cite

Background Recently, several studies have investigated the relationship between Pre‐miR‐27a rs895819 polymorphism and risk of various cancers. However, the relationship between rs895819 and diffuse large B‐cell lymphoma (DLBCL) has not been well known. Methods In this study, we conducted a case‐control study to explore the role of Pre‐miR‐27a rs895819 in risk of DLBCL. The PCR‐TaqMan and luciferase assays and in vitro experiments were used to evaluate polymorphism function. Results As a result, we found subjects carrying with rs895819 AG/GG genotype had a significantly decreased risk when compared with those carrying the AA genotype. Further qPCR assay showed that the DLBCL patients carrying AG/GG genotypes showed a lower level of mature miR‐27a when compared with patients carrying AA genotype. Moreover, miR‐27a levels were upregulated in DLBCL tissues compared with normal lymphoid tissues. Further in vitro experiments showed that miR‐27a might function as an oncogene through target TGFBR1. In addition, TGFBR1 overexpression rescues effects of miR‐27a inhibitor on DLBCL cells phenotypes. Conclusions In conclusion, these findings indicate that rs895819 A > G might reduce the expression of mature miR‐27a, and leading a higher level of TGFBR1, ultimately inhibiting the development of DLBCL.

show abstract

TGF-β receptors: In and beyond TGF-β signaling

Cited by 356 publications

References 113 publications

Odontogenic infection by Porphyromonas gingivalis exacerbates fibrosis in NASH via hepatic stellate cell activation

Odontogenic infection by Porphyromonas gingivalis exacerbates fibrosis in NASH via hepatic stellate cell activation

S-endoglin expression is induced in hyperoxia and contributes to altered pulmonary angiogenesis in bronchopulmonary dysplasia development

Pre‐miR‐27a rs895819 polymorphism and risk of diffuse large B‐cell lymphoma

Contact Info

Product

Resources

About