Fibulin-2 is a key mediator of the pro-neurogenic effect of TGF-beta1 on adult neural stem cells

Radice, Pablo Daniel; Mathieu, Patricia; Leal, María Celeste; Farias, Marta Cristina Vieira; Ferrari, Carina Cintia; Puntel, Mariana; Salibe, Mariano; Chernomoretz, Ariel; Pitossi, Fernando Juan

doi:10.1016/j.mcn.2015.06.004

Cited by 22 publications

(21 citation statements)

References 34 publications

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“…Collectively, it is plausible that ECM environment altered by upregulated fibulin-2 contributes, in part, to the pathogenesis of human heart failure via enhancing myocardial TGF-β activation via positive feedback loop. The same principle of autoregulation is also noted in neuronal tissues, where fibulin-2 mediates TGF-β-induced proneurogenic effects in the rat model in vivo and in vitro [ 138 ].…”

Section: Interaction Between Fibulins and Tgf-βmentioning

confidence: 91%

Extracellular Interactions between Fibulins and Transforming Growth Factor (TGF)-β in Physiological and Pathological Conditions

Tsuda

2018

IJMS

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Transforming growth factor (TGF)-β is a multifunctional peptide growth factor that has a vital role in the regulation of cell growth, differentiation, inflammation, and repair in a variety of tissues, and its dysregulation mediates a number of pathological conditions including fibrotic disorders, chronic inflammation, cardiovascular diseases, and cancer progression. Regulation of TGF-β signaling is multifold, but one critical site of regulation is via interaction with certain extracellular matrix (ECM) microenvironments, as TGF-β is primarily secreted as a biologically inactive form sequestrated into ECM. Several ECM proteins are known to modulate TGF-β signaling via cell–matrix interactions, including thrombospondins, SPARC (Secreted Protein Acidic and Rich in Cystein), tenascins, osteopontin, periostin, and fibulins. Fibulin family members consist of eight ECM glycoproteins characterized by a tandem array of calcium-binding epidermal growth factor-like modules and a common C-terminal domain. Fibulins not only participate in structural integrity of basement membrane and elastic fibers, but also serve as mediators for cellular processes and tissue remodeling as they are highly upregulated during embryonic development and certain disease processes, especially at the sites of epithelial–mesenchymal transition (EMT). Emerging studies have indicated a close relationship between fibulins and TGF-β signaling, but each fibulin plays a different role in a context-dependent manner. In this review, regulatory interactions between fibulins and TGF-β signaling are discussed. Understanding biological roles of fibulins in TGF-β regulation may introduce new insights into the pathogenesis of some human diseases.

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Section: Interaction Between Fibulins and Tgf-βmentioning

confidence: 91%

Extracellular Interactions between Fibulins and Transforming Growth Factor (TGF)-β in Physiological and Pathological Conditions

Tsuda

2018

IJMS

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“…Correspondingly, disruption of TGF beta signaling in Ltbp1-null mice results in reduced snout length and a more compact head shape (Drews et al 2008). Bioavailability of TGF beta ligands is further influenced by other fibrillin-interacting proteins, such as fibulins (Harikrishnan et al 2015;Radice et al 2015;Tian et al 2015). Genes encoding two fibulins (Fbln2 and Fbln5) were also associated with TWARs (TWAR15.Chr6 and TWAR8.Chr12, respectively).…”

Section: Wwwgenomeorgmentioning

confidence: 99%

Widespread cis-regulatory convergence between the extinct Tasmanian tiger and gray wolf

2019

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The extinct marsupial Tasmanian tiger, or thylacine, and the eutherian gray wolf are among the most widely recognized examples of convergent evolution in mammals. Despite being distantly related, these large predators independently evolved extremely similar craniofacial morphologies, and evidence suggests that they filled similar ecological niches. Previous analyses revealed little evidence of adaptive convergence between their protein-coding genes. Thus, the genetic basis of their convergence is still unclear. Here, we identified candidate craniofacial cis-regulatory elements across vertebrates and compared their evolutionary rates in the thylacine and wolf, revealing abundant signatures of convergent positive selection. Craniofacial thylacine-wolf accelerated regions were enriched near genes involved in TGF beta (TGFB) and BMP signaling, both of which are key morphological signaling pathways with critical roles in establishing the identities and boundaries between craniofacial tissues. Similarly, enhancers of genes involved in craniofacial nerve development showed convergent selection and involvement in these pathways. Taken together, these results suggest that adaptation in cis-regulators of TGF beta and BMP signaling may provide a mechanism to explain the coevolution of developmentally and functionally integrated craniofacial structures in these species. We also found that despite major structural differences in marsupial and eutherian brains, accelerated regions in both species were common near genes with roles in brain development. Our findings support the hypothesis that, relative to protein-coding genes, positive selection on cis-regulatory elements is likely to be an essential driver of adaptive convergent evolution and may underpin thylacine-wolf phenotypic similarities.

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“…Interestingly, fibulin-3 does not bind TGF-b1 appreciably, but instead interacts with the type I receptor TbRI/ ALK-5 and blocks formation of a functional ligand -receptor complex (Tian et al 2015). Other fibulins may also regulate TGF-b signaling (Renard et al 2010;Radice et al 2015), but the underlying molecular mechanism has not been elucidated.…”

Section: Fibulins (Fblns)mentioning

confidence: 99%

Agonists and Antagonists of TGF-β Family Ligands

Chang

2016

Cold Spring Harb Perspect Biol

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The discovery of the transforming growth factor β (TGF-β) family ligands and the realization that their bioactivities need to be tightly controlled temporally and spatially led to intensive research that has identified a multitude of extracellular modulators of TGF-β family ligands, uncovered their functions in developmental and pathophysiological processes, defined the mechanisms of their activities, and explored potential modulator-based therapeutic applications in treating human diseases. These studies revealed a diverse repertoire of extracellular and membrane-associated molecules that are capable of modulating TGF-β family signals via control of ligand availability, processing, ligand-receptor interaction, and receptor activation. These molecules include not only soluble ligand-binding proteins that were conventionally considered as agonists and antagonists of TGF-β family of growth factors, but also extracellular matrix (ECM) proteins and proteoglycans that can serve as "sink" and control storage and release of both the TGF-β family ligands and their regulators. This extensive network of soluble and ECM modulators helps to ensure dynamic and cell-specific control of TGF-β family signals. This article reviews our knowledge of extracellular modulation of TGF-β growth factors by diverse proteins and their molecular mechanisms to regulate TGF-β family signaling.

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Fibulin-2 is a key mediator of the pro-neurogenic effect of TGF-beta1 on adult neural stem cells

Cited by 22 publications

References 34 publications

Extracellular Interactions between Fibulins and Transforming Growth Factor (TGF)-β in Physiological and Pathological Conditions

Extracellular Interactions between Fibulins and Transforming Growth Factor (TGF)-β in Physiological and Pathological Conditions

Widespread cis-regulatory convergence between the extinct Tasmanian tiger and gray wolf

Agonists and Antagonists of TGF-β Family Ligands

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