scholarly journals Role of bone morphogenetic proteins in adrenal physiology and disease

2010 ◽  
Vol 44 (4) ◽  
pp. 203-211 ◽  
Author(s):  
Inga K Johnsen ◽  
Felix Beuschlein
Keyword(s):  
Bone Morphogenetic Proteins ◽  
Regulatory Networks ◽  
Transforming Growth Factor ◽  
Large Body ◽  
Transforming Growth Factor Β ◽  
Therapeutic Approaches ◽  
Bmp Signalling ◽  
Type Specification ◽  
Adrenocortical Tumour

Bone morphogenetic proteins (BMPs) are members of the transforming growth factor-β superfamily of ligands that impact on a multitude of biological processes including cell type specification, differentiation and organogenesis. Furthermore, a large body of evidence points towards important BMP-dependent mechanisms in tumorigenesis. In accordance with their diverse actions, BMPs have been demonstrated to serve as auto-, para- and endocrine modulators also in a number of hormonal systems. In this review, we highlight novel aspects of BMP-dependent regulatory networks that pertain to adrenal physiology and disease, which have been uncovered during recent years. These aspects include the role of BMP-dependent mechanism during adrenal development, modulating effects on catecholamine synthesis and steroidogenesis and dysregulation of BMP signalling in adrenal tumorigenesis. Furthermore, we summarize potential therapeutic approaches that are based on reconstitution of BMP signalling in adrenocortical tumour cells.

Heparin/heparan sulphate binding in the TGF-β cytokine superfamily

2006 ◽  
Vol 34 (3) ◽  
pp. 458-460 ◽  
Author(s):  
C.C. Rider
Keyword(s):  
Bone Morphogenetic Proteins ◽  
Transforming Growth Factor ◽  
Heparan Sulphate ◽  
Transforming Growth Factor Β ◽  
Cell Types ◽  
Binding Properties ◽  
And Migration ◽  
Close Relatives ◽  
Bmp Antagonist

The TGF-β (transforming growth factor-β) cytokine superfamily in mammals contains some 30 members. These dimeric proteins are characterized by a strongly conserved cystine knot-based structure. They regulate the proliferation, differentiation and migration of many cell types, and therefore have important roles in morphogenesis, organogenesis, tissue maintenance and wound healing. Thus far, around one-quarter of these cytokines have been shown to bind to heparin and heparan sulphate. Well-established examples are the TGF-β isoforms 1 and 2, and the BMPs (bone morphogenetic proteins) -2 and -4. In studies in my laboratory, we have shown that GDNF (glial-cell-line-derived neurotrophic factor) and its close relatives neurturin and artemin bind to heparin and heparan sulphate with high affinity. We have reported previously that binding of GDNF is highly dependent on the presence of 2-O-sulphate groups. More recently, we and others have been investigating the heparin/heparan sulphate-binding properties of BMP-7, which is a representative of a distinct BMP subgroup from that of BMPs -2 and -4. Interestingly, several of the various specific BMP antagonist proteins also bind to heparin and heparan sulphate. Much remains to be learnt about the nature and role of glycosaminoglycan interactions in the TGF-β superfamily, but current work suggests that these cytokines do not share a single highly conserved heparin/heparan sulphate-binding site.

scholarly journals Eps15R is required for bone morphogenetic protein signalling and differentially compartmentalizes with Smad proteins

Open Biology ◽  
2012 ◽  
Vol 2 (4) ◽  
pp. 120060 ◽  
Author(s):  
Elizabeth M. Callery ◽  
Chong Yon Park ◽  
Xin Xu ◽  
Haitao Zhu ◽  
James C. Smith ◽  
...  
Keyword(s):  
Growth Factor ◽  
Bone Morphogenetic Proteins ◽  
Egf Receptor ◽  
Transforming Growth Factor ◽  
Adaptor Protein ◽  
Transforming Growth Factor Β ◽  
Morphogenetic Protein ◽  
Smad Proteins ◽  
Epidermal Growth ◽  
Bmp Signalling

Transforming growth factor β superfamily members signal through Smad transcription factors. Bone morphogenetic proteins (BMPs) act via Smads 1, 5 and 8 and TGF-βs signal through Smads 2 and 3. The endocytic adaptor protein Eps15R, or ‘epidermal growth factor (EGF) receptor pathway substrate 15-related protein’ is a component of EGF signal transduction, mediating internalization of the EGF receptor. We show that it interacts with Smad proteins, is required for BMP signalling in animal caps and stimulates Smad1 transcriptional activity. This function resides in the Asp-Pro-Phe motif-enriched ‘DPF domain’ of Eps15R, which activates transcription and antagonizes Smad2 signalling. In living cells, Eps15R segregates into spatially distinct regions with different Smads, indicating an unrecognized level of Smad compartmentalization.

scholarly journals The Role of BMP Signaling in Female Reproductive System Development and Function

2021 ◽  
Vol 22 (21) ◽  
pp. 11927
Author(s):  
Esmeralda Magro-Lopez ◽  
María Ángeles Muñoz-Fernández
Keyword(s):  
Bone Morphogenetic Proteins ◽  
Reproductive System ◽  
Transforming Growth Factor ◽  
Current Knowledge ◽  
System Development ◽  
Transforming Growth Factor Β ◽  
Bmp Signaling ◽  
Female Reproductive System ◽  
And Function

Bone morphogenetic proteins (BMPs) are a group of multifunctional growth factors that belong to the transforming growth factor-β (TGF-β) superfamily of proteins. Originally identified by their ability to induce bone formation, they are now known as essential signaling molecules that regulate the development and function of the female reproductive system (FRS). Several BMPs play key roles in aspects of reproductive system development. BMPs have also been described to be involved in the differentiation of human pluripotent stem cells (hPSCs) into reproductive system tissues or organoids. The role of BMPs in the reproductive system is still poorly understood and the use of FRS tissue or organoids generated from hPSCs would provide a powerful tool for the study of FRS development and the generation of new therapeutic perspectives for the treatment of FRS diseases. Therefore, the aim of this review is to summarize the current knowledge about BMP signaling in FRS development and function.

scholarly journals Emerging roles of the bone morphogenetic protein pathway in cancer: potential therapeutic target for kinase inhibition

2016 ◽  
Vol 44 (4) ◽  
pp. 1117-1134 ◽  
Author(s):  
Pawina Jiramongkolchai ◽  
Philip Owens ◽  
Charles C. Hong
Keyword(s):  
Bone Morphogenetic Proteins ◽  
Therapeutic Target ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Cell Types ◽  
Tumour Microenvironment ◽  
Bone Morphogenetic Protein Pathway ◽  
Bmp Signalling ◽  
Unique Cell ◽  
The Impact

Bone morphogenetic proteins (BMPs) belong to the transforming growth factor-β (TGF-β) family signalling pathway. Similar to TGF-β, the complex roles of BMPs in development and disease are demonstrated by their dichotomous roles in various cancers and cancer stages. Although early studies implicated BMP signalling in tumour suppressive phenotypes, the results of more recent experiments recognize BMPs as potent tumour promoters. Many of these complexities are becoming illuminated by understanding the role of BMPs in their contextual role in unique cell types of cancer and the impact of their surrounding tumour microenvironment. Here we review the emerging roles of BMP signalling in cancer, with a focus on the molecular underpinnings of BMP signalling in individual cancers as a valid therapeutic target for cancer prevention and treatment.

scholarly journals TGFβ/BMP Signaling Pathway in Cartilage Homeostasis

Cells ◽  
2019 ◽  
Vol 8 (9) ◽  
pp. 969 ◽  
Author(s):  
Nathalie Thielen ◽  
Peter van der Kraan ◽  
Arjan van Caam
Keyword(s):  
Bone Morphogenetic Proteins ◽  
Transforming Growth Factor ◽  
Articular Chondrocytes ◽  
Family Members ◽  
Transforming Growth Factor Β ◽  
Bmp Signaling ◽  
Cartilage Homeostasis ◽  
Cartilage Biology ◽  
Matrix Production

Cartilage homeostasis is governed by articular chondrocytes via their ability to modulate extracellular matrix production and degradation. In turn, chondrocyte activity is regulated by growth factors such as those of the transforming growth factor β (TGFβ) family. Members of this family include the TGFβs, bone morphogenetic proteins (BMPs), and growth and differentiation factors (GDFs). Signaling by this protein family uniquely activates SMAD-dependent signaling and transcription but also activates SMAD-independent signaling via MAPKs such as ERK and TAK1. This review will address the pivotal role of the TGFβ family in cartilage biology by listing several TGFβ family members and describing their signaling and importance for cartilage maintenance. In addition, it is discussed how (pathological) processes such as aging, mechanical stress, and inflammation contribute to altered TGFβ family signaling, leading to disturbed cartilage metabolism and disease.

scholarly journals Role of bone morphogenetic proteins in periodontal regeneration- a review

2016 ◽  
Vol 4 (2) ◽  
pp. 141
Author(s):  
Santhi Priya Potharaju ◽  
Santha Kumari Prathypaty ◽  
Ravi Kanth Chintala ◽  
Durga Bai Yendluri ◽  
Jai Krishna Srikanth Kolliboyana
Keyword(s):  
Bone Morphogenetic Proteins ◽  
Transforming Growth Factor ◽  
Scientific Evidence ◽  
Periodontal Regeneration ◽  
Mesenchymal Cell ◽  
Transforming Growth Factor Β ◽  
Clinical Applications ◽  
Unique Property ◽  
Osteogenic Cells

Bone Morphogenetic Proteins (BMPs) are multifunctional growth factors and have the unique property of inducing stem and mesenchymal cell differentiation in to osteogenic cells, capable of producing bone. They are categorized under the super family Transforming Growth Factor-β (TGF-β). In the concept of tissue engineering they are the first approved therapeutic proteins to be used in conjunction with a scaffold and a biocompatible fixative device. Thus in this review the mechanism of action of BMPs is described at its cellular and molecular levels along with its potential clinical applications, utilization perspectives and scientific evidence in periodontal regeneration.

scholarly journals Interference RNA-based silencing of endogenous SMAD4 in porcine granulosa cells resulted in decreased FSH-mediated granulosa cells proliferation and steroidogenesis

Reproduction ◽  
2011 ◽  
Vol 141 (5) ◽  
pp. 643-651 ◽  
Author(s):  
Wei Wang ◽  
Xia Chen ◽  
Xinxiu Li ◽  
Li Wang ◽  
Haiyan Zhang ◽  
...  
Keyword(s):  
Bone Morphogenetic Proteins ◽  
Granulosa Cells ◽  
Transforming Growth Factor ◽  
Critical Role ◽  
Signal Transduction Pathway ◽  
Transforming Growth Factor Β ◽  
Porcine Granulosa Cells ◽  
Cell Growth And Differentiation ◽  
Interference Rna

FSH plays a critical role in granulosa cell (GC) proliferation and steroidogenesis through modulation by factors including bone morphogenetic proteins family, which belongs to transforming growth factor β (TGFB) superfamily. TGFBs are the key factors in maintaining cell growth and differentiation in ovaries. However, the interaction of FSH and TGFB on the GCs' proliferation and steroidogenesis remains to be elucidated. In this study, we have investigated the role of SMAD4, a core molecule mediating the intracellular TGFB/SMAD signal transduction pathway, in FSH-mediated proliferation and steroidogenesis of porcine GCs. In this study, SMAD4 was knocked down using interference RNA in porcine GCs. Our results showed that SMAD4-siRNA causes specific inhibition of SMAD4 mRNA and protein expression after transfection. Knockdown of SMAD4 significantly inhibited FSH-induced porcine GC proliferation and estradiol production and changed the expression of cyclin D2, CDK2, CDK4, CYP19a1, and CYP11a1. Thus, these observations establish an important role of SMAD4 in the regulation of the response of porcine GCs to FSH.

scholarly journals Optogenetic control of the Bone Morphogenetic Protein signalling pathway through engineered blue light-sensitive receptors

2020 ◽  
Author(s):  
Paul A. Humphreys ◽  
Steven Woods ◽  
Christopher A. Smith ◽  
Stuart A. Cain ◽  
Robert Lucas ◽  
...  
Keyword(s):  
Blue Light ◽  
Bone Morphogenetic Proteins ◽  
Target Genes ◽  
Transforming Growth Factor ◽  
Nuclear Translocation ◽  
Transforming Growth Factor Β ◽  
Signalling Pathway ◽  
Bmp Signalling ◽  
Optogenetic Control

AbstractBone Morphogenetic Proteins (BMPs) are members of the Transforming Growth Factor β (TGFβ) superfamily and have crucial roles during development; including mesodermal patterning and specification of renal, hepatic and skeletal tissues. In vitro developmental models currently rely upon costly and unreliable recombinant BMP proteins that do not enable dynamic or precise perturbation of the BMP signalling pathway. Here, we develop a novel optogenetic BMP signalling system (optoBMP) that enables rapid induction of the canonical BMP signalling pathway through illumination with blue light. We demonstrate the utility of the optoBMP system in multiple human cell lines to initiate signal transduction through phosphorylation and nuclear translocation of SMAD1/5, leading to upregulation of BMP target genes including Inhibitors of DNA binding ID2 and ID4. Furthermore, we demonstrate how the optoBMP system can be used to fine-tune activation of the BMP signalling pathway through variable light stimulation. Optogenetic control of BMP signalling will enable dynamic and high-throughput intervention across a variety of applications in cellular and developmental systems.

scholarly journals Pancreatic Cancer and Therapy: Role and Regulation of Cancer Stem Cells

2021 ◽  
Vol 22 (9) ◽  
pp. 4765
Author(s):  
Susmita Barman ◽  
Iram Fatima ◽  
Amar B. Singh ◽  
Punita Dhawan
Keyword(s):  
Pancreatic Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Signaling Pathways ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Therapeutic Approaches ◽  
Cancer Types ◽  
Pancreatic Cancer Stem Cells

Despite significant improvements in clinical management, pancreatic cancer (PC) remains one of the deadliest cancer types, as it is prone to late detection with extreme metastatic properties. The recent findings that pancreatic cancer stem cells (PaCSCs) contribute to the tumorigenesis, progression, and chemoresistance have offered significant insight into the cancer malignancy and development of precise therapies. However, the heterogeneity of cancer and signaling pathways that regulate PC have posed limitations in the effective targeting of the PaCSCs. In this regard, the role for K-RAS, TP53, Transforming Growth Factor-β, hedgehog, Wnt and Notch and other signaling pathways in PC progression is well documented. In this review, we discuss the role of PaCSCs, the underlying molecular and signaling pathways that help promote pancreatic cancer development and metastasis with a specific focus on the regulation of PaCSCs. We also discuss the therapeutic approaches that target different PaCSCs, intricate mechanisms, and therapeutic opportunities to eliminate heterogeneous PaCSCs populations in pancreatic cancer.

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