TGFbeta reviews

INTRODUCTION: The potent profibrotic cytokine transforming growth factor-β (TGF-β) has been associated with the onset and progression of the fibrosis seen in the autoimmune connective tissue disease scleroderma (systemic sclerosis, SSc). AREA COVERED: This review explores the data supporting the notion that TGF-β contributes to SSc fibrosis and examines why initiating clinical trials in SSc aimed at targeting integrin-mediated latent TGF-β activation is timely...

INTRODUCTION: Osteoarthritis is a heterogeneous joint disorder that lacks a clinically meaningful disease modifying drug. Animal models have been beneficial in understanding basic joint pathology and providing rationale for future clinical trials on identified targets. This review aims to discuss promising therapeutic targets of osteoarthritis that are currently in animal studies or early clinical trials. AREAS COVERED: PubMed was searched for articles published between 2017 and 2021 with the following terms: (osteoarthritis AND autophagy) OR (osteoarthritis AND senescence) OR (osteoarthritis AND TGFbeta) OR (osteoarthritis AND EGFR) OR (osteoarthritis AND Wnt/β-catenin) OR (osteoarthritis AND inflammation)...

For over 60 years, selenium (Se) has been known as an essential microelement to many biological functions, including cardiovascular homeostasis. This review presents a compilation of studies conducted in the past 20 years related to chronic Chagas disease cardiomyopathy (CCC), caused by Trypanosoma cruzi infection, a neglected disease that represents a global burden, especially in Latin America. Experimental and clinical data indicate that Se may be used as a complementary therapy to prevent heart failure and improve heart function...

The beating heart is subject to intrinsic mechanical factors, exerted by contraction of the myocardium (stretch and strain) and fluid forces of the enclosed blood (wall shear stress). The earliest contractions of the heart occur already in the 10-somite stage in the tubular as yet unsegmented heart. With development, the looping heart becomes asymmetric providing varying diameters and curvatures resulting in unequal flow profiles. These flow profiles exert various wall shear stresses and as a consequence different expression patterns of shear responsive genes...

PURPOSE: The purpose of this article is to assemble, review, and provide a synopsis of the historical and current literature regarding optimal sequencing of radiation (RT) and immunotherapy combination treatments. MATERIALS AND METHODS: A review of the literature was performed using PubMed with the query "radiation" and "Immunotherapy", "PD1", "PDL1", "CTLA4", "OX40", "checkpoint", "vaccine", "macrophage", "STING", and "TGFbeta". Studies that included sequencing of therapy were evaluated and the studies were included at the authors discretion...

Tendons and ligaments are connective tissues that have been comparatively less studied than muscle and cartilage/bone, even though they are crucial for proper function of the musculoskeletal system. In tendon biology, considerable progress has been made in identifying tendon-specific genes (Scleraxis, Mohawk, and Tenomodulin) in the past decade. However, besides tendon function and the knowledge of a small number of important players in tendon biology, neither the ontogeny of the tenogenic lineage nor signaling cascades have been fully understood...

Liver fibrosis and in particular cirrhosis are the major causes of morbidity and mortality of patients with chronic liver disease. Their prevention or reversal have become major endpoints in clinical trials with novel liver specific drugs. Remarkable progress has been made with therapies that efficiently address the cause of the underlying liver disease, as in chronic hepatitis B and C. Highly effective antiviral therapy can prevent progression or even induce reversal in the majority of patients, but such treatment remains elusive for the majority of liver patients with advanced alcoholic or nonalcoholic steatohepatitis, genetic or autoimmune liver diseases...

Ischemic heart disease remains the leading cause of death worldwide. Ischemic pre-, post-, and remote conditionings trigger endogenous cardioprotection that renders the heart resistant to ischemic-reperfusion injury (IRI). Mimicking endogenous cardioprotection by modulating genes involved in cardioprotective signal transduction provides an opportunity to reproduce endogenous cardioprotection with better possibilities of translation into the clinical setting. Genes and signaling pathways by which conditioning maneuvers exert their effects on the heart are partially understood...

PURPOSE OF REVIEW: It is well established that blocking the renin-angiotensin-aldosterone system (RAAS) is effective for the treatment of cardiovascular and renal complications in hypertension and diabetes mellitus. Although the induction of transforming growth factor beta1 (TGFbeta1) by components of the RAAS mediates the hypertrophic and fibrogenic changes in cardiovascular-renal complications, it is still controversial as to whether TGFbeta1 can be a target to prevent such complications...

A key question for urologic practitioners is whether an apparently organ-confined prostate cancer (PCa) is actually aggressive or not. The dilemma is to specifically identify among all prostate tumors the very aggressive high-grade cancers that will become life-threatening by developing extra-prostatic invasion and metastatic potential and the indolent cancers that will never modify a patient's life expectancy. A choice must be made between several therapeutic options to achieve the optimal personalized management of the disease that causes as little harm as possible to patients...

Marfan syndrome is an autosomal dominant disorder, characterized by tall stature, long arms and legs, ectopia lentis, and aortic aneurysms and dissections. Recent research has revealed that these phenotypes are caused by mutations in fibrillin-1, the major structural component of elastic microfibrils, and the continuing dysregulation of transforming growth factor beta (TGFbeta) signaling is principally considered to be contributing to the pathophysiological background of the disease. Blockade of TGFbeta signaling by angiotensin II receptor antagonism is a novel promising therapeutic option, and thus such large clinical randomized controlled trials are underway...

Diabetes mellitus (DM) is a chronic metabolic disease characterized by the presence of hyperglycemia, which can lead to many complications over time. These complications, such as nephropathy, retinopathy, neuropathy, impaired wound healing and accelerated atherosclerosis, are implicated with a large number of cellular and subcellular changes on vessels. In agreement, evidence indicates that in retinopathy, nephropathy and atherosclerotic plaque, there is excessive angiogenesis, whereas in wound healing and myocardial perfusion, blood vessel growth is impaired...

Regulatory T cells (Tregs) play a crucial role in the maintenance of immune homeostasis. The two best studied types of CD4(+) regulatory T cells are the Foxp3(+) Tregs and the T regulatory type 1 (Tr1) cells. CD4(+) regulatory T cells play a protective role in autoimmune disease. On the other hand, they also may have pathogenic properties in infectious diseases and carcinogenesis. Because of their potential for the therapy of various human diseases, factors responsible for expanding regulatory T cells are of interest...

Transforming growth factor-beta (TGFbeta) is an immunosuppressive cytokine produced by tumour cells and immune cells that can polarize many components of the immune system. This Review covers the effects of TGFbeta on natural killer (NK) cells, dendritic cells, macrophages, neutrophils, CD8(+) and CD4(+) effector and regulatory T cells, and NKT cells in animal tumour models and in patients with cancer. Collectively, many recent studies favour the hypothesis that blocking TGFbeta-induced signalling in the tumour microenvironment enhances antitumour immunity and may be beneficial for cancer therapy...

In the past, most scientists conducted their inquiries of nature via inductivism, the patient accumulation of "pieces of information" in the pious hope that the sum of the parts would clarify the whole. Increasingly, modern biology employs the tools of bioinformatics and systems biology in attempts to reveal the "big picture." Most successful laboratories engaged in the pursuit of the secrets of embryonic development, particularly those whose research focus is craniofacial development, pursue a middle road where research efforts embrace, rather than abandon, what some have called the "pedestrian" qualities of inductivism, while increasingly employing modern data mining technologies...

Fibrosis is one of the largest groups of diseases for which there is no therapy but is believed to occur because of a persistent tissue repair program. During connective tissue repair, "activated" fibroblasts migrate into the wound area, where they synthesize and remodel newly created extracellular matrix. The specialized type of fibroblast responsible for this action is the alpha-smooth muscle actin (alpha-SMA)-expressing myofibroblast. Abnormal persistence of the myofibroblast is a hallmark of fibrotic diseases...

One of the most frequent types of organ damage developing in the course of hypertension is left ventricular hypertrophy (LVH). The percentage of hypertensive patients with LVH, assessed with echocardiographic method, amounts to 20-60%, depending on blood pressure level and duration of hypertension. This review includes current opinions on the role of transforming growth factor Beta1 (TGFP31), basic fibroblast growth factor (bFGF, FGF2), and insulin-like growth factor-1 (IGF-1) in the development of LVH in the course of hypertension...

The third lineage of T helper subsets, Th17, has recently been identified as an IL- 17-producing CD4+ Th cell, and its functions and regulatory mechanisms have been extensively characterized in immune responses. Functional studies have provided evidence that Th17 cells are important for the modulation of autoimmune responses, such as chronic asthma, rheumatoid arthritis, inflammatory bowel diseases, and multiple sclerosis. Murine Th17 cell differentiation is enhanced by the coordinated functions of distinct cytokines including TGFbeta, IL-6, IL-21, and IL-23, whereas IL-2, IL-4, IFNgamma, and IL-27 inhibit its differentiation...

During human embryogenesis, differentiation of haematopoietic stem cells (HSCs) and their progeny is regulated spatially and temporally. In the adult, hemopoiesis is restricted to bone marrow (BM) which contains HSCs residing within the so-called 'niches'. These are microenvironments consisting of extracellular matrix (ECM) macromolecules (mainly glycosaminoglycans, proteoglycans, fibronectin and collagens) and stromal cells that act in concert to keep HSCs in quiescence or to promote their growth and differentiation, since BM stromal cells secrete specific growth factors acting on responsive stem cells...

The distortion of growth factor signalling is the most important prerequisite in tumour progression. Transforming growth factor-beta (TGFbeta) signalling regulates tumour progression by a tumour cell-autonomous mechanism or through tumour-stroma interaction, and has either a tumour-suppressing or tumour-promoting function depending on cellular context. Such inherent complexity of TGFbeta signalling results in arduous, but promising, assignments for developing therapeutic strategies against malignant tumours...