Signaling Pathways That Control Rho Kinase Activity Maintain the Embryonic Epicardial Progenitor State

Artamonov, Mykhaylo V.; Jin, Li; Franke, Aaron S.; Momotani, Ko; Ho, Ruoya; Dong, Xiaoxin; Majesky, Mark W.; Somlyo, Avril V.

doi:10.1074/jbc.m114.613190

Cited by 12 publications

(14 citation statements)

References 63 publications

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“…The interaction between myocardial VCAM‐1 and epicardial α4β1 integrin seems to be involved in this stabilization (Dettman et al, ), probably by inhibiting cytoskeletal changes (Dokic and Dettman, ). These changes can be related with the control of RhoA/Rho kinase activity, which has been recently involved in the maintenance of the epicardial EMT (Artamonov et al, ).…”

Section: The Best Known: Epicardial‐derived Cells In Cardiac Developmentmentioning

confidence: 99%

Coelomic epithelium‐derived cells in visceral morphogenesis

Ariza

Carmona

Cañete

et al. 2015

Developmental Dynamics

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Coelomic cavities of vertebrates are lined by a mesothelium which develops from the lateral plate mesoderm. During development, the coelomic epithelium is a highly active cell layer, which locally is able to supply mesenchymal cells that contribute to the mesodermal elements of many organs and provide signals which are necessary for their development. The relevance of this process of mesenchymal cell supply to the developing organs is becoming clearer because genetic lineage tracing techniques have been developed in recent years. Body wall, heart, liver, lungs, gonads, and gastrointestinal tract are populated by cells derived from the coelomic epithelium which contribute to their connective and vascular tissues, and sometimes to specialized cell types such as the stellate cells of the liver, the Cajal interstitial cells of the gut or the Sertoli cells of the testicle. In this review we collect information about the contribution of coelomic epithelium derived cells to visceral development, their developmental fates and signaling functions. The common features displayed by all these processes suggest that the epithelial-mesenchymal transition of the embryonic coelomic epithelium is an underestimated but key event of vertebrate development, and probably it is shared by all the coelomate metazoans. Developmental Dynamics 245:307-322, 2016. V C 2015 Wiley Periodicals, Inc.

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Section: The Best Known: Epicardial‐derived Cells In Cardiac Developmentmentioning

confidence: 99%

Coelomic epithelium‐derived cells in visceral morphogenesis

Ariza

Carmona

Cañete

et al. 2015

Developmental Dynamics

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“…Defining the role for EPAC in the transition of epicardial cells to coronary smooth muscle cells demonstrated a dependence on RhoA/ROCK activity (638) and a similar inhibitory nature of cAMP activation to attenuate TGF-␤1-induced EMT (545,906). In support of a suppressive role for EPAC/Rap1 in EMT, TGF-␤1 treatment is observed to increase PDE4D mRNA while decreasing Rap1A and EPAC expression (34,1171). In contrast to TGF-␤1 stimulation, direct EPAC activation in epicardial cells suppressed markers of smooth muscle, smooth muscle protein 22 (SM22), and smooth muscle actin (SMA) and maintained cell-cell contacts suggesting prevention of EMT.…”

Section: Proliferation/differentiationmentioning

confidence: 99%

“…In contrast to TGF-␤1 stimulation, direct EPAC activation in epicardial cells suppressed markers of smooth muscle, smooth muscle protein 22 (SM22), and smooth muscle actin (SMA) and maintained cell-cell contacts suggesting prevention of EMT. These effects were echoed by the inhibition of PDE (34). Thus the suppressive action of cAMP on EMT and EPAC/Rap1 roles could again be targeted to decrease fibrosis and promote healing of affected hearts.…”

Section: Proliferation/differentiationmentioning

confidence: 99%

Intracellular cAMP Sensor EPAC: Physiology, Pathophysiology, and Therapeutics Development

Robichaux

Cheng

2018

Physiological Reviews

158

226

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This review focuses on one family of the known cAMP receptors, the exchange proteins directly activated by cAMP (EPACs), also known as the cAMP-regulated guanine nucleotide exchange factors (cAMP-GEFs). Although EPAC proteins are fairly new additions to the growing list of cAMP effectors, and relatively "young" in the cAMP discovery timeline, the significance of an EPAC presence in different cell systems is extraordinary. The study of EPACs has considerably expanded the diversity and adaptive nature of cAMP signaling associated with numerous physiological and pathophysiological responses. This review comprehensively covers EPAC protein functions at the molecular, cellular, physiological, and pathophysiological levels; and in turn, the applications of employing EPAC-based biosensors as detection tools for dissecting cAMP signaling and the implications for targeting EPAC proteins for therapeutic development are also discussed.

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“…These proteins affect pathways including canonical and non-canonical Wnt signalling and hedgehog and retinoic acid signalling, which have downstream effects on gene programmes that regulate intercellular interactions, actin dynamics and cell motility. Following invagination of mesenchyme from the embryonic epicardium into the myocardium, various signal transduction and regulatory molecules, including TGFβ, 54, 55 FGF, 56 platelet derived growth factor (PDGF), 57 proto-oncogene tyrosine-protein kinase, 55 rho kinase, 58 integrins, 59 popeye domain-containing genes such as Bves, 60, 61 serum response factor, 62 transcription factor 21 (Tcf21), 63, 64 and myocardin-related factors 65 govern the transition of epicardium derived cells (EPDCs) into cells with more mature fates, including fibroblasts. 5, 6 There is also evidence from studies in Xenopus laevis that Tcf21 functions as a transcriptional repressor to regulate proepicardial cell specification and the correct formation of a mature epithelial epicardium.…”

Section: Fibroblasts and Adult Myocardial Homeostasismentioning

confidence: 99%

Novel therapeutic strategies targeting fibroblasts and fibrosis in heart disease

Gourdie

Dimmeler

Kohl

2016

Nat Rev Drug Discov

268

204

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Our understanding of cardiac fibroblast functions has moved beyond their roles in heart structure and extracellular matrix generation, and now includes contributions to paracrine, mechanical and electrical signalling during ontogenesis and normal cardiac activity. Fibroblasts have central roles in pathogenic remodelling during myocardial ischaemia, hypertension and heart failure. As key contributors to scar formation, they are crucial for tissue repair after interventions including surgery and ablation. Novel experimental approaches targeting cardiac fibroblasts are promising potential therapies for heart disease. Indeed, several existing drugs act, at least partially, through effects on cardiac connective tissue. This Review outlines the origins and roles of fibroblasts in cardiac development, homeostasis and disease; illustrates the involvement of fibroblasts in current and emerging clinical interventions; and identifies future targets for research and development.

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Signaling Pathways That Control Rho Kinase Activity Maintain the Embryonic Epicardial Progenitor State

Cited by 12 publications

References 63 publications

Coelomic epithelium‐derived cells in visceral morphogenesis

Coelomic epithelium‐derived cells in visceral morphogenesis

Intracellular cAMP Sensor EPAC: Physiology, Pathophysiology, and Therapeutics Development

Novel therapeutic strategies targeting fibroblasts and fibrosis in heart disease

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