Transcription factors—Intricate players of the bone morphogenetic protein signaling pathway

Ampuja, Minna; Kallioniemi, Anne

doi:10.1002/gcc.22502

Cited by 9 publications

(5 citation statements)

References 123 publications

(201 reference statements)

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“…An unbiased search for signalling pathways using the Reactome pathway database (Reactome Version 70) (Fabregat et al , 2018) contained the term “SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription” (Fig 9A) as significantly upregulated in DIE astrocytes, with Sp1 , Smad7 , Ccnt2 showing higher expression in these astrocytes. Smads are TFs acting as down‐stream effectors in TGFβ or/and BMP signalling (Luo, 2017; Ampuja & Kallioniemi, 2018; Dituri et al , 2019), and both of these signalling pathways regulate NSC properties, including quiescence (Mira et al , 2010) as well as astrocyte differentiation during development (Mabie et al , 1997; Stipursky et al , 2014). Smad4, a common TGFβ/BMP signalling mediator, is expressed across all DIE astrocyte clusters (Fig 9B).…”

Section: Resultsmentioning

confidence: 99%

Molecular diversity of diencephalic astrocytes reveals adult astrogenesis regulated by Smad4

et al. 2021

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Astrocytes regulate brain-wide functions and also show regionspecific differences, but little is known about how general and region-specific functions are aligned at the single-cell level. To explore this, we isolated adult mouse diencephalic astrocytes by ACSA-2-mediated magnetic-activated cell sorting (MACS). Singlecell RNA-seq revealed 7 gene expression clusters of astrocytes, with 4 forming a supercluster. Within the supercluster, cells differed by gene expression related to ion homeostasis or metabolism, with the former sharing gene expression with other regions and the latter being restricted to specific regions. All clusters showed expression of proliferation-related genes, and proliferation of diencephalic astrocytes was confirmed by immunostaining. Clonal analysis demonstrated low level of astrogenesis in the adult diencephalon, but not in cerebral cortex grey matter. This led to the identification of Smad4 as a key regulator of diencephalic astrocyte in vivo proliferation and in vitro neurosphere formation. Thus, astrocytes show diverse gene expression states related to distinct functions with some subsets being more widespread while others are more regionally restricted. However, all share low-level proliferation revealing the novel concept of adult astrogenesis in the diencephalon.

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Section: Resultsmentioning

confidence: 99%

Molecular diversity of diencephalic astrocytes reveals adult astrogenesis regulated by Smad4

et al. 2021

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“…25 MH2 domains are expressed in all eight Smads and are responsible for interaction with BMP receptors, interaction with DNA-binding proteins, and transcriptional activation. 25 Many transcription factors have been identified that regulate BMP target genes, although further work is needed to establish if these are universal regulators of BMP signaling or context-dependent in their mode of action, as reviewed in detail by Ampuja et al 26 For example, the transcription factor ATF2 was shown to activate the promoter of β-myosin heavy chain, important in cardiac development. 27 Several pathways have also been identified that signal in a Smad-independent manner (Figure 1), known as noncanonical pathways.…”

Section: Canonical and Noncanonical Pathwaysmentioning

confidence: 99%

The Role of Bone Morphogenetic Proteins in Diabetic Complications

Perera

Ritchie

Tate

2019

ACS Pharmacol. Transl. Sci.

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The prevalence of diabetes has reached epidemic proportions and is placing a significant burden on healthcare systems globally. Diabetes has a detrimental impact on many organs in the human body, including accelerating the development of micro-and macrovascular complications. Current therapeutic options to treat diabetic complications have their limitations. Importantly, many slow but fail to reverse the progression of diabetic complications. Bone morphogenetic proteins (BMPs) are a highly conserved subgroup of the transforming growth factor β (TGFβ) superfamily, signaling via serine/threonine kinase receptors, that have recently been implicated in glucose homeostasis and insulin resistance in the setting of diabetes. Downstream of the receptors, the signal can be transduced via the canonical Smaddependent pathway or the noncanonical Smad-independent pathways. BMPs are essential in organ development, tissue homeostasis, and, as expected, disease pathogenesis. In fact, deletion of BMPs can be embryonically lethal or result in severe organ abnormalities. This review outlines the BMP signaling pathway and its relevance to diabetic complications, namely, diabetic nephropathy, diabetes-associated cardiovascular diseases, and diabetic retinopathy. Understanding the complexities of BMP signaling and particularly its tissue-, cellular-, and time-dependent actions will help delineate the underlying pathogenesis of the disease and may ultimately be harnessed in the treatment of diabetes-induced complications. This would replicate progress made in numerous other diseases, including cancer and atherosclerosis.

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“…Bone morphogenetic proteins (BMPs), included in the transforming growth factor beta (TGFβ) superfamily, are involve from embryogenesis to adult organ cell homeostasis [1][2][3][4][5]. Initially described in bone formation [6], this protein group is divided into at least four subgroups with similar functions and biochemical structures [2].…”

Section: Introductionmentioning

confidence: 99%

Correlation between intestinal BMP2, IFNγ, and neural death in experimental infection with Trypanosoma cruzi

et al. 2021

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Megacolon is one of the main late complications of Chagas disease, affecting approximately 10% of symptomatic patients. However, studies are needed to understand the mechanisms involved in the progression of this condition. During infection by Trypanosoma cruzi (T. cruzi), an inflammatory profile sets in that is involved in neural death, and this destruction is known to be essential for megacolon progression. One of the proteins related to the maintenance of intestinal neurons is the type 2 bone morphogenetic protein (BMP2). Intestinal BMP2 homeostasis is directly involved in the maintenance of organ function. Thus, the aim of this study was to correlate the production of intestinal BMP2 with immunopathological changes in C57Bl/6 mice infected with the T. cruzi Y strain in the acute and chronic phases. The mice were infected with 1000 blood trypomastigote forms. After euthanasia, the colon was collected, divided into two fragments, and a half was used for histological analysis and the other half for BMP2, IFNγ, TNF-α, and IL-10 quantification. The infection induced increased intestinal IFNγ and BMP2 production during the acute phase as well as an increase in the inflammatory infiltrate. In contrast, a decreased number of neurons in the myenteric plexus were observed during this phase. Collagen deposition increased gradually throughout the infection, as demonstrated in the chronic phase. Additionally, a BMP2 increase during the acute phase was positively correlated with intestinal IFNγ. In the same analyzed period, BMP2 and IFNγ showed negative correlations with the number of neurons in the myenteric plexus. As the first report of BMP2 alteration after infection by T. cruzi, we suggest that this imbalance is not only related to neuronal damage but may also represent a new route for maintaining the intestinal proinflammatory profile during the acute phase.

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Transcription factors—Intricate players of the bone morphogenetic protein signaling pathway

Abstract: Bone morphogenetic proteins (BMPs) are a family of growth factors, some of which are known by the name growth and differentiation factor (GDF). BMPs were discovered in the 1960s in an attempt to find factors capable of inducing bone formation. By the end of 1980s, several different

Cited by 9 publications

References 123 publications

Molecular diversity of diencephalic astrocytes reveals adult astrogenesis regulated by Smad4

Molecular diversity of diencephalic astrocytes reveals adult astrogenesis regulated by Smad4

The Role of Bone Morphogenetic Proteins in Diabetic Complications

Correlation between intestinal BMP2, IFNγ, and neural death in experimental infection with Trypanosoma cruzi

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