Transforming growth factor‐β and bone morphogenetic proteins: Cooperative players in chick and murine programmed retinal cell death

Franke, Andreas G.; Gubbe, Christian; Beier, M.; Duenker, Nicole

doi:10.1002/cne.20869

Cited by 37 publications

(40 citation statements)

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“…TGF-β is known as a contextually acting molecule that cooperates with other cytokines, including TNF-α and BMPs, to induce apoptosis (Franke et al 2006;Schuster et al 2003). In the present study, we show that another cytokine of the TGF-β superfamily, ActivinA, also induces apoptosis in oligodendroglial progenitor cells (Fig.…”

Section: Activina Induces Apoptosis In Oligodendroglial Progenitor Cellssupporting

confidence: 61%

“…Chen et al 2002Chen et al , 2006. TGF-βs are also involved in developmental and neuronal apoptosis and cooperate with other secreted cytokines such as BMPs or TNF-α (Böttner et al 2000;Duenker and Krieglstein 2000Duenker et al 2002a, b;Franke et al 2006;Sanchez-Capelo 2005;Schuster et al 2003;Schuster and Krieglstein 2002;Unsicker and Strelau 2000). The importance of TGF-βs during neural ontogenetic cell death was first shown in chicken, where apoptosis is reduced in various neuron populations by immunoneutralisation of endogenous TGF-βs .…”

Section: Introductionmentioning

confidence: 99%

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TGF-β superfamily members, ActivinA and TGF-β1, induce apoptosis in oligodendrocytes by different pathways

et al. 2008

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Activins and transforming growth factor (TGF)-βs, members of the TGF-β superfamily, affect numerous physiological processes, including apoptosis, in a variety of organs and tissues. Apoptotic functions of TGF-βs, in contrast to those of the activins, are well documented in the developing and adult nervous system. TGF-βs operate in a contextdependent manner and cooperate with other cytokines in the regulation of apoptosis. In this study, we show, for the first time, an apoptotic function of ActivinA in the nervous system, i.e. in oligodendroglial progenitor cells. Using the oligodendroglial cell line OLI-neu, we show that ActivinA acts autonomously, without cooperating with TGF-β. In contrast to the mechanism of TGF-β-mediated apoptosis involving Bcl-xl down-regulation, Bcl-xl in ActivinA-induced apoptosis is classically sequestered by the BH3-only protein Puma.Puma expression is controlled by the transcription factor p53 as demonstrated by experiments with the p53 inhibitor Pifithrin-α. Furthermore, in the apoptotic TGF-β pathway, caspase-3 is activated, whereas in the apoptotic ActivinA pathway, apoptosis-inducing factor is released to trigger DNA fragmentation. These data suggest that TGF-β and ActivinA induce apoptosis in oligodendrocytes by different apoptotic pathways.

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Section: Activina Induces Apoptosis In Oligodendroglial Progenitor Cellssupporting

confidence: 61%

Section: Introductionmentioning

confidence: 99%

TGF-β superfamily members, ActivinA and TGF-β1, induce apoptosis in oligodendrocytes by different pathways

et al. 2008

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“…This result would argue that BMP is directly involved in inducing the apoptotic pathway at later stages. Moreover, BMPs have been shown to induce apoptosis in the developing retina (10,19), further supporting our results.…”

Section: Q-t)supporting

confidence: 90%

BMP signaling mediates stem/progenitor cell-induced retina regeneration

Haynes

Gutierrez

Aycinena

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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We identified a mechanism whereby retina regeneration in the embryonic chick can be induced by the contribution of stem/ progenitor cells. We show that bone morphogenetic protein (BMP) signaling is sufficient and necessary to induce retina regeneration and that its action can be divided into two phases. By 3 days after postretinectomy (d PR), the BMP pathway directs proliferation and regeneration through the activation of Smad (canonical BMP pathway) and the up-regulation of FGF signaling by the MAPK pathway. By 7d PR, it induces apoptosis by activating p38 (a noncanonical BMP pathway) and down-regulating FGF signaling (by both MAPK and AKT pathways). Apoptosis at this later stage can be prevented, and BMP-induced regeneration can be further induced by inhibition of p38. These results unravel a mechanism for stem/ progenitor cell-mediated retina regeneration, where BMP activation establishes a cross-talk with the FGF pathway and selectively activates the canonical and noncanonical BMP pathways. Retina stem/progenitor cells exist in other species, including humans. Thus, our findings provide insights on how retinal stem cells can be activated for possible regenerative therapies.p38 ͉ FGF B one morphogenetic proteins (BMPs) are secreted signaling proteins that elicit their effect by binding to a heterodimer receptor complex composed of a BMP type I receptor (BMPRIA or BMPRIB) and a BMP type II receptor (BMPRII) (1). The BMP pathway can activate the canonical downstream effector, Smad, or a noncanonical downstream effector, transforming growth factor-␤-activated kinase (TAK1) (1). Several endogenous inhibitors, including noggin, chordin, follistatin, and gremlin, can regulate the ability of BMP to activate these pathways (2).In the developing retina, BMP2, BMP4, and BMP7, as well as the BMP receptors, are expressed in the chick (3) and mouse (4-6) and have been found to play a role in establishing the dorsal/ventral patterning of the retina. They also regulate the differentiation and survival of retinal neurons (7-11). Because of the BMP pathway's importance during retina development and in stem cell biology, we wanted to examine its role in inducing and regulating retina regeneration.A population of retinal stem cells is maintained after retinal development in the anterior margin of the eye in many vertebrates, including humans (12, 13). In most vertebrates, these retinal stem cells remain quiescent and do not respond to injury. However, cells in the anterior margin of the embryonic chick eye respond to injury during a limited time of retina development, providing an opportunity to study the induction process of these stem/progenitor cells (13-15).The embryonic chick has been shown to regenerate a complete retina in Ϸ7 days as long as a retinectomy is performed on or around embryonic day 4 (E4) and a source of FGF is added (14,16,17). In the presence of ectopic FGF2, regeneration takes place by transdifferentiation of the retinal pigmented epithelium (RPE) and the activation of retinal stem/progenitor cells (RS/ R...

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“…Unfortunately, no other cytokine is known to induce apoptosis by an unique pathway in OLI-neu cells. All studied cytokines cooperate with TGF-b to increase signaling and use the same pathways (Franke et al, 2006;Schuster et al, 2003). Therefore, Staurosporine (STS) was used as a general apoptosis inducer.…”

Section: Tgf-b-induced Fractin-bcl-xl Binding Occurs In Oligodendroglmentioning

confidence: 99%

Involvement of fractin in TGF‐β‐induced apoptosis in oligodendroglial progenitor cells

Schulz

Vogel

Mashima

et al. 2009

Glia

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Transforming growth factor-beta (TGF-beta) induces apoptotic cell death during the development of the nervous system. We recently identified that TGF-beta induced apoptosis in oligodendroglial progenitor cells (primary cells as well as oligodendroglial cell line OLI-neu) is characterized by down-regulation of Bcl-xl. In this report, we now focused on mechanisms that mediate TGF-beta dependent Bcl-xl down-regulation in oligodendroglial cells. We showed that the caspase-specific cleavage product Fractin is produced in oligodendroglial cells during TGF-beta-mediated apoptosis, which represents an early event of the cascade. Cleavage of actin into Fractin was dependent on functional actin and caspases, and occurred simultaneously with a Fractin-Bcl-xl-interaction. This Fractin-Bcl-xl interaction indicated a connection between Bcl-xl down-regulation and Fractin appearance, since Bcl-xl regulation was also dependent on caspases and functional actin, and an overexpression of Fractin induced a Bcl-xl protein down-regulation. Further analysis of Fractin-Bcl-xl interaction in other culture systems confirmed these data. In conclusion, we show that Fractin is not only an apoptotic marker, but has indeed a functional role in apoptotic signaling in oligodendrocytes.

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Transforming growth factor‐β and bone morphogenetic proteins: Cooperative players in chick and murine programmed retinal cell death

Cited by 37 publications

References 53 publications

TGF-β superfamily members, ActivinA and TGF-β1, induce apoptosis in oligodendrocytes by different pathways

TGF-β superfamily members, ActivinA and TGF-β1, induce apoptosis in oligodendrocytes by different pathways

BMP signaling mediates stem/progenitor cell-induced retina regeneration

Involvement of fractin in TGF‐β‐induced apoptosis in oligodendroglial progenitor cells

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