TGFbeta reviews

The ability of bone-marrow-derived mesenchymal stem cells (MSCs) and adipose-derived stem cells (ASCs) to undergo chondrogenic differentiation has been studied extensively, and it has been suggested that the chondrogenic potential of these stem cells differ from each other. Here, we provide a comprehensive review and analysis of the various growth factor induction agents for MSC and ASC three-dimensional in vitro chondrogenic differentiation. In general, the most common growth factors for chondrogenic induction come from the transforming growth factor beta (TGFbeta) superfamily...

Bone morphogenetic proteins (BMPs) are phylogenetically conserved signaling molecules that belong to the TGFbeta superfamily and are involved in the morphogenesis, as well as the pathogenesis, of several disorders. The function of BMPs is regulated by BMP antagonists that bind directly to the proteins, thus inhibiting binding to the relevant receptors. Pharmacological doses of BMP-7 have been demonstrated to repair established renal injury and, thus, BMP antagonists modulating endogenous BMP-7 activities may be possible therapeutic targets for kidney disease...

The type III transforming growth factor-beta receptor (TGFbetaR3, betaglycan), a tumour suppressor, is the most frequently lost TGFbeta pathway component. This event appears to be very important in the transition of the TGFbeta pathway from having tumour-suppressor activity in early prostate tumour development, to having tumour-promoting activity in metastatic disease. Moreover, loss of the TGFbetaR3 can also affect the cellular response towards testosterone, inhibin/activin, and dysregulate growth-factor pathways that mediate growth and angiogenesis...

Epithelial-mesenchymal transition (EMT), a process by which differentiated epithelial cells undergo a phenotypic conversion that gives rise to the matrix-producing fibroblasts and myofibroblasts, is increasingly recognized as an integral part of tissue fibrogenesis after injury. However, the degree to which this process contributes to kidney fibrosis remains a matter of intense debate and is likely to be context-dependent. EMT is often preceded by and closely associated with chronic interstitial inflammation and could be an adaptive response of epithelial cells to a hostile or changing microenvironment...

The TGFbeta superfamily growth factor BMP7 performs essential biological functions in embryonic development and regeneration of injured tissue in the adult. BMP7 activity is regulated at numerous levels in the signaling pathway by the expression of extracellular antagonists, decoy receptors and inhibitory cell signaling components. Additionally, expression of the BMP7 gene is tightly controlled both during embryonic development and adult life. In this review, the current status of work on regulation of BMP7 at the genomic level is discussed...

Recent increase in human lifespan has shifted the spectrum of aging-related disorders to an unprecedented upsurge in cardiovascular diseases, especially calcific aortic valve stenosis, which has an 80% risk of progression to heart failure and death. A current therapeutic option for calcified valves is surgical replacement, which provides only temporary relief. Recent progress in cardiovascular research has suggested that arterial and valve calcification are the result of an active process of osteogenic differentiation, induced by a pro-atherogenic inflammatory response...

Smad proteins are intracellular molecules that mediate the canonical signaling cascade of TGFbeta superfamily growth factors. The TGFbeta superfamily comprises two groups of growth factors, BMPs and TGFbetas. Both groups can be further divided into several sub-groups based on sequence homologies and functional similarities. Ligands of the TGFbeta superfamily bind to cell surface receptors to activate Smad proteins in the cytoplasm; then the activated Smad proteins translocate into the nucleus to activate or repress specific target gene transcription...

Molecular imaging of breast cancer can potentially be used for breast cancer screening, staging, restaging, response evaluation and guiding therapies. Techniques for molecular breast cancer imaging include magnetic resonance imaging (MRI), optical imaging, and radionuclide imaging with positron emission tomography (PET) or single photon emission computed tomography (SPECT). This review focuses on PET and SPECT imaging which can provide sensitive serial non invasive information of tumor characteristics. Most clinical data are gathered on the visualization of general processes such as glucose metabolism with the PET-tracer [(18)F]fluorodeoxyglucose (FDG) and DNA synthesis with [18F]fluoro-L-thymidine (FLT)...

Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide, with a median survival of 6-16 m. Factors responsible for the poor prognosis include late onset diagnosis, underlying cirrhosis and resistance to chemotherapy; 40% of HCCs are clonal and therefore potentially arise from progenitor/stem cells. New insights are provided from several signaling pathways, such as STAT3, NOTCH, hedgehog and transforming growth factor-beta (TGFbeta), which are involved in stem cell renewal, differentiation, survival, and are commonly deregulated in HCC...

microRNAs (miRNAs) are small, non-coding RNAs that modulate diverse biological functions through the repression of target genes. miRNA profiling studies have indicated that the levels of miRNAs are altered during normal development and pathogenesis of various diseases, including cancer and cardiovascular disorders. The signaling pathways which control miRNA biogenesis and the mechanisms of regulation, however, are not well understood. Following transcription, mature miRNAs are generated through a series of coordinated processing events mediated by large protein complexes...

Ligands of the Transforming Growth Factor type beta (TGFbeta) family exert multiple and sometimes opposite effects on most cell types in vivo depending on cellular context, which mainly includes the stage of the target cell, the local environment of this cell or niche, and the identity and the dosage of the ligand. Significant progress has been made in the molecular dissection of the regulation of the activity of the ligands and their intracellular signal transduction pathways, including via the canonical Smad pathway where Smads interact with many transcription factors...

In recent years, informatics studies have predicted several new ways in which the transforming growth factor beta (TGFbeta) signaling pathway can be post-translationally regulated. Subsequently, many of these predictions were experimentally validated. These approaches include phylogenetic predictions for the phosphorylation, sumoylation and ubiquitylation of pathway components, as well as kinetic models of endocytosis, phosphorylation and nucleo-cytoplasmic shuttling. We review these studies and provide a brief ;how to' guide for phylogenetics...

Transforming growth factor beta (TGFbeta) pathways are implicated in metazoan development, adult homeostasis and disease. TGFbeta ligands signal via receptor serine/threonine kinases that phosphorylate, and activate, intracellular Smad effectors as well as other signaling proteins. Oligomeric Smad complexes associate with chromatin and regulate transcription, defining the biological response of a cell to TGFbeta family members. Signaling is modulated by negative-feedback regulation via inhibitory Smads. We review here the mechanisms of TGFbeta signal transduction in metazoans and emphasize events crucial for embryonic development...

Foxp3(+) regulatory T cells (T(regs)) contribute significantly to the maintenance of peripheral tolerance, but they ultimately fail in autoimmune diseases. The events that lead to T(reg) failure in controlling autoreactive effector T cells (T(effs)) during autoimmunity are not completely understood. In this review, we discuss possible mechanisms for this subversion as they relate to type 1 diabetes (T1D) and multiple sclerosis (MS). Recent studies emphasize firstly, the role of inflammatory cytokines, such as IL-6, in inhibiting or subverting T(reg) function; secondly, the issue of T(reg) plasticity; thirdly, the possible resistance of autoimmune T cells to T(reg)-mediated control; and fourthly, T(reg)-associated inhibitory cytokines TGFbeta, IL-10 and IL-35 in facilitating T(reg) suppressive activity and promoting T(reg) generation...

Transforming growth factor-beta (TGFbeta) is a secreted cytokine, which intricately controls a plethora of physiological and pathological processes during development and carcinogenesis. TGFbeta exerts antiproliferative effects and functions as a tumor suppressor during early stages of tumorigenesis, whereas at later stages it functions as a tumor promoter aiding in metastatic progression through an autocrine TGFbeta loop. Intricate knowledge of TGFbeta signaling and its regulation are still evolving. In this review, we make an attempt to showcase the associated enigma of TGFbeta signaling in its dual functional role as tumor suppressor and metastatic promoter during early and late stages of carcinogenesis, respectively...

BACKGROUND: microRNAs (miRNAs) are short, single-stranded RNAs that regulate gene expression at the post-transcriptional level. Recent research has shown that miRNAs and their target mRNAs are differentially expressed in endometriosis and other disorders of the female reproductive system. Since miRNAs control a broad spectrum of normal and pathological cellular functions, they may play pivotal roles in the pathogenesis of these disorders. METHODS: A systematic review was undertaken of the published literature on; (i) the expression and functions of miRNAs in mammalian female reproductive tissues with a focus on endometriosis and the malignancies and fertility disorders related to this disease; and (ii) the potential roles played by validated mRNA targets of endometriosis-associated miRNAs...

Early in animal development, gradients of secreted morphogenic molecules, such as Sonic hedgehog (Shh), Wnt and TGFbeta/Bmp family members, regulate cell proliferation and determine the fate and phenotype of the target cells by activating well-characterized signalling pathways, which ultimately control gene transcription. Shh, Wnt and TGFbeta/Bmp signalling also play an important and evolutionary conserved role in neural circuit assembly. They regulate neuronal polarization, axon and dendrite development and synaptogenesis, processes that require rapid and local changes in cytoskeletal organization and plasma membrane components...

Clusterin, also known as apolipoprotein J, is a versatile chaperone molecule which contains several amphipathic and coiled-coil alpha-helices, typical characteristics of small heat shock proteins. In addition, clusterin has three large intrinsic disordered regions, so-called molten globule domains, which can stabilize stressed protein structures. Twenty years ago, it was demonstrated that the expression of clusterin was clearly increased in Alzheimer's disease (AD). Later it was observed that clusterin can bind amyloid-beta peptides and prevent their fibrillization...

Tumour necrosis factor alpha (TNF-alpha) is a prototypic pro-inflammatory cytokine that has a central role in the initial host response to Mycobacterium tuberculosis infection. It is a key player in granuloma formation, macrophage activation, bacterial killing, and pathology in vivo. However, the exact mechanism has not been completely understood. This review summarizes the TNFalpha data acquired from the 'gold standard' guinea pig animal model of tuberculosis. While production of TNFalpha is widely accepted as beneficial to the host response, we have found that this hypothesis is just one side of the story...

Bone morphogenetic proteins (BMPs) are multifunctional growth factors belonging to the transforming growth factor beta (TGFbeta) superfamily. Recent observations clearly emphasize the emerging role of BMPs in angiogenesis: (i) two genetic vascular diseases (hereditary hemorrhagic telangiectasia (HHT) and pulmonary arterial hypertension (PAH)) are caused by mutations in genes encoding components of the BMP signalling pathway (endoglin, ALK1 and BMPRII). (ii) BMP9 has been identified as the physiological ligand of the endothelial receptor ALK1 in association with BMPRII...