TGFβ attenuates tumour response to PD-L1 blockade by contributing to exclusion of T cells

Nature, Год журнала: 2018, Номер 554(7693), С. 544 - 548

Опубликована: Фев. 1, 2018

Язык: Английский

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New insights into TGF-β/Smad signaling in tissue fibrosis

Chemico-Biological Interactions, Год журнала: 2018, Номер 292, С. 76 - 83

Опубликована: Июль 11, 2018

Язык: Английский

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Specificity, versatility, and control of TGF-β family signaling

Science Signaling, Год журнала: 2019, Номер 12(570)

Опубликована: Фев. 26, 2019

Encoded in mammalian cells by 33 genes, the transforming growth factor-β (TGF-β) family of secreted, homodimeric and heterodimeric proteins controls differentiation most, if not all, cell lineages many aspects tissue physiology multicellular eukaryotes. Deregulation TGF-β signaling leads to developmental anomalies disease, whereas enhanced contributes cancer fibrosis. Here, we review fundamentals mechanisms that are initiated upon ligand binding its surface receptors dependence responses on input from cooperation with other pathways. We discuss how exquisitely control functional presentation activation heteromeric receptor complexes transmembrane, dual-specificity kinases and, thus, define their context-dependent responsiveness ligands. also introduce through which called Smads act as intracellular effectors ligand-induced gene expression show specificity impressive versatility Smad depend cross-talk Last, non-Smad mechanisms, distinct ligand-activated complexes, complement thus contribute cellular responses.

Язык: Английский

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TGF-β Signaling

Biomolecules, Год журнала: 2020, Номер 10(3), С. 487 - 487

Опубликована: Март 23, 2020

Transforming growth factor-β (TGF-β) represents an evolutionarily conserved family of secreted polypeptide factors that regulate many aspects physiological embryogenesis and adult tissue homeostasis. The TGF-β members are also involved in pathophysiological mechanisms underlie diseases. Although the comprises factors, which exhibit cell type-specific developmental stage-dependent biological actions, they all signal via signaling pathways. controlled at extracellular level, where ligand secretion, deposition to matrix activation prior play important roles. At plasma membrane TGF-βs associate with receptor kinases mediate phosphorylation-dependent downstream mediators, mainly SMAD proteins, oligomerization-dependent ubiquitin ligases intracellular protein kinases. interplay between SMADs other proteins regulatory signals control expression target genes, RNA processing multiple levels, mRNA translation nuclear or cytoplasmic regulation. This article emphasizes importance biochemical executing functions by prototype member family, TGF-β.

Язык: Английский

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Signaling pathways and targeted therapy for myocardial infarction

Signal Transduction and Targeted Therapy, Год журнала: 2022, Номер 7(1)

Опубликована: Март 10, 2022

Abstract Although the treatment of myocardial infarction (MI) has improved considerably, it is still a worldwide disease with high morbidity and mortality. Whilst there long way to go for discovering ideal treatments, therapeutic strategies committed cardioprotection cardiac repair following ischemia are emerging. Evidence pathological characteristics in MI illustrates cell signaling pathways that participate survival, proliferation, apoptosis, autophagy cardiomyocytes, endothelial cells, fibroblasts, monocytes, stem cells. These include key players inflammation response, e.g., NLRP3/caspase-1 TLR4/MyD88/NF-κB; crucial mediators oxidative stress instance, Notch, Hippo/YAP, RhoA/ROCK, Nrf2/HO-1, Sonic hedgehog; controller fibrosis such as TGF-β/SMADs Wnt/β-catenin; main regulator angiogenesis, PI3K/Akt, MAPK, JAK/STAT, hedgehog, etc. Since play an important role administering process MI, aiming at targeting these aberrant improving manifestations indispensable promising. Hence, drug therapy, gene protein exosome therapy have been emerging known novel therapies. In this review, we summarize by regulating associated pathways, which contribute inhibiting cardiomyocytes death, attenuating inflammation, enhancing so re-functionalize damaged hearts.

Язык: Английский

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Zinc in Wound Healing Modulation

Nutrients, Год журнала: 2017, Номер 10(1), С. 16 - 16

Опубликована: Дек. 24, 2017

Wound care is a major healthcare expenditure. Treatment of burns, surgical and trauma wounds, diabetic lower limb ulcers skin wounds medical challenge with current therapies largely focused on supportive measures. Successful wound repair requires series tightly coordinated steps including coagulation, inflammation, angiogenesis, new tissue formation extracellular matrix remodelling. Zinc an essential trace element (micronutrient) which plays important roles in human physiology. cofactor for many metalloenzymes required cell membrane repair, proliferation, growth immune system function. The pathological effects zinc deficiency include the occurrence lesions, retardation, impaired function compromised would healing. Here, we discuss investigations cellular molecular mechanisms modulating healing process. Knowledge gained from this body research will help to translate these findings into future clinical management

Язык: Английский

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Tissue-specific contribution of macrophages to wound healing

Seminars in Cell and Developmental Biology, Год журнала: 2016, Номер 61, С. 3 - 11

Опубликована: Авг. 11, 2016

Macrophages are present in all tissues, either as resident cells or monocyte-derived that infiltrate into tissues. The tissue site largely determines the phenotype of tissue-resident cells, which help to maintain homeostasis and act sentinels injury. Both recruited macrophages make a substantial contribution wound healing following In this review, we evaluate how two fundamentally distinct i.e. lung skin, differentially contribute process healing. We highlight commonalities macrophage functions during repair contrast them with distinct, tissue-specific fulfill different stages

Язык: Английский

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TGF-β Signaling in Lung Health and Disease

International Journal of Molecular Sciences, Год журнала: 2018, Номер 19(8), С. 2460 - 2460

Опубликована: Авг. 20, 2018

Transforming growth factor (TGF)-β is an evolutionarily conserved pleiotropic that regulates a myriad of biological processes including development, tissue regeneration, immune responses, and tumorigenesis. TGF-β necessary for lung organogenesis homeostasis as evidenced by genetically engineered mouse models. crucial epithelial-mesenchymal interactions during branching morphogenesis alveolarization. Expression activation the three ligand isoforms in lungs are temporally spatially regulated multiple mechanisms. The structurally exposed to extrinsic stimuli pathogens, susceptible inflammation, allergic reactions, carcinogenesis. Upregulation ligands observed major pulmonary diseases, fibrosis, emphysema, bronchial asthma, cancer. cellular such suppression epithelial cells, alveolar cell differentiation, fibroblast activation, extracellular matrix organization. These effects closely associated with remodeling fibrosis emphysema. also central T deeply involved asthmatic airway inflammation. most potent inducer transition non-small cancer cells pivotal development tumor-promoting microenvironment tissue. This review summarizes integrates current knowledge signaling relevant health disease.

Язык: Английский

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TGF-β1 – A truly transforming growth factor in fibrosis and immunity

Seminars in Cell and Developmental Biology, Год журнала: 2019, Номер 101, С. 123 - 139

Опубликована: Дек. 24, 2019

Язык: Английский

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Cytokine signature associated with disease severity in chronic fatigue syndrome patients

Proceedings of the National Academy of Sciences, Год журнала: 2017, Номер 114(34)

Опубликована: Июль 31, 2017

Significance Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) devastates the lives of millions people and has remained a mystery illness despite decades research. It long been suspected that inflammation is central to its pathogenesis. Although only two cytokines were found be different (TGF-β higher resistin lower) in ME/CFS patients compared with controls, 17 correlated severity. Thirteen these are proinflammatory may contribute many symptoms experience for several years. Only CXCL9 (MIG) inversely duration.

Язык: Английский

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