Role of myosin light chain kinase in cardiotrophin-1-induced cardiac myofibroblast cell migration

Freed, Darren H.; Chilton, Lisa; Li, Yun; Dangerfield, Aran L.; Raizman, Joshua E.; Rattan, Sunil G.; Visen, N.S.; Hryshko, Larry V.; Dixon, Ian M.C.

doi:10.1152/ajpheart.01041.2010

Cited by 28 publications

(22 citation statements)

References 62 publications

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“…Leukotrienes, generated through 5-lipoxygenase (5-LOX)-mediated actions may act, at least in part, by promoting fibroblast migration [77]. Cytokines (such as IL-1 and cardiotrophin-1) [78], [79], and growth factors (such as TGF-β and FGFs) [63], may also induce fibroblast migration into the site of infarction. Movement of fibroblasts in the highly plastic and dynamic environment of the infarct requires adhesive interactions of the fibroblasts with the surrounding matrix that may involve integrin signaling.…”

Section: Fibroblasts During the Proliferative Phasementioning

confidence: 99%

Fibroblasts in myocardial infarction: A role in inflammation and repair

Shinde

Frangogiannis

2014

Journal of Molecular and Cellular Cardiology

416

373

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Fibroblasts do not only serve as matrix-producing reparative cells, but exhibit a wide range of functions in inflammatory and immune responses, angiogenesis and neoplasia. The adult mammalian myocardium contains abundant fibroblasts enmeshed within the interstitial and perivascular extracellular matrix. The current review manuscript discusses the dynamic phenotypic and functional alterations of cardiac fibroblasts following myocardial infarction. Extensive necrosis of cardiomyocytes in the infarcted heart triggers an intense inflammatory reaction. In the early stages of infarct healing, fibroblasts become pro-inflammatory cells, activating the inflammasome and producing cytokines, chemokines and proteases. Pro-inflammatory cytokines (such as Interleukin-1) delay myofibroblast transformation, until the wound is cleared from dead cells and matrix debris. Resolution of the inflammatory infiltrate is associated with fibroblast migration, proliferation, matrix protein synthesis and myofibroblast conversion. Growth factors and matricellular proteins play an important role in myofibroblast activation during the proliferative phase of healing. Formation of a mature cross-linked scar is associated with clearance of fibroblasts, as poorly-understood inhibitory signals restrain the fibrotic response. However, in the non-infarcted remodeling myocardium, local fibroblasts may remain activated in response to volume and pressure overload and may promote interstitial fibrosis. Considering their abundance, their crucial role in cardiac inflammation and repair, and their involvement in myocardial dysfunction and arrhythmogenesis, cardiac fibroblasts may be key therapeutic targets in cardiac remodeling.

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Section: Fibroblasts During the Proliferative Phasementioning

confidence: 99%

Fibroblasts in myocardial infarction: A role in inflammation and repair

Shinde

Frangogiannis

2014

Journal of Molecular and Cellular Cardiology

416

373

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“…MLCK is a CaM-dependent kinase that plays a fundamental role regulating cell migration and function as a key player in smooth, skeletal, and cardiac muscle contraction (reviewed in [41,100,101]). Inhibition of MLCK and CaM by specific inhibitors (ML-7 and W-7, respectively), prevents the migration of myofibroblasts induced by cardiotrophin-1 participating in the repair of scars after infarction [68]. Dupuytren's disease is an idiopathic fibroproliferative condition characterized by the formation of nodular lesions in the palmar fascia where the accumulation of fibroblasts and highly contractile myofibroblasts severely alters the function of the hands (reviewed in [102]).…”

Section: Cam and Cytoskeleton Dynamicsmentioning

confidence: 99%

The Role of Calmodulin in Tumor Cell Migration, Invasiveness, and Metastasis

Villalobo

Berchtold

2020

IJMS

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Calmodulin (CaM) is the principal Ca2+ sensor protein in all eukaryotic cells, that upon binding to target proteins transduces signals encoded by global or subcellular-specific changes of Ca2+ concentration within the cell. The Ca2+/CaM complex as well as Ca2+-free CaM modulate the activity of a vast number of enzymes, channels, signaling, adaptor and structural proteins, and hence the functionality of implicated signaling pathways, which control multiple cellular functions. A basic and important cellular function controlled by CaM in various ways is cell motility. Here we discuss the role of CaM-dependent systems involved in cell migration, tumor cell invasiveness, and metastasis development. Emphasis is given to phosphorylation/dephosphorylation events catalyzed by myosin light-chain kinase, CaM-dependent kinase-II, as well as other CaM-dependent kinases, and the CaM-dependent phosphatase calcineurin. In addition, the role of the CaM-regulated small GTPases Rac1 and Cdc42 (cell division cycle protein 42) as well as CaM-binding adaptor/scaffold proteins such as Grb7 (growth factor receptor bound protein 7), IQGAP (IQ motif containing GTPase activating protein) and AKAP12 (A kinase anchoring protein 12) will be reviewed. CaM-regulated mechanisms in cancer cells responsible for their greater migratory capacity compared to non-malignant cells, invasion of adjacent normal tissues and their systemic dissemination will be discussed, including closely linked processes such as the epithelial–mesenchymal transition and the activation of metalloproteases. This review covers as well the role of CaM in establishing metastatic foci in distant organs. Finally, the use of CaM antagonists and other blocking techniques to downregulate CaM-dependent systems aimed at preventing cancer cell invasiveness and metastasis development will be outlined.

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“…Myosin light chain kinase is activated by Ca 2+ /calmodulin in myofibroblasts [48] and smooth muscle [1]. Furthermore, myosin light chain kinase is necessary for migration of various cell types including muscle cells [45, 48]. …”

Section: Roles Of Dynamic Actin Cytoskeleton and Actin-associated Promentioning

confidence: 99%

The roles and regulation of the actin cytoskeleton, intermediate filaments and microtubules in smooth muscle cell migration

2017

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Smooth muscle cell migration has been implicated in the development of respiratory and cardiovascular systems; and airway/vascular remodeling. Cell migration is a polarized cellular process involving a protrusive cell front and a retracting trailing rear. There are three cytoskeletal systems in mammalian cells: the actin cytoskeleton, the intermediate filament network, and microtubules; all of which regulate all or part of the migrated process. The dynamic actin cytoskeleton spatially and temporally regulates protrusion, adhesions, contraction, and retraction from the cell front to the rear. c-Abl tyrosine kinase plays a critical role in regulating actin dynamics and migration of airway smooth muscle cells and nonmuscle cells. Recent studies suggest that intermediate filaments undergo reorganization during migration, which coordinates focal adhesion dynamics, cell contraction, and nucleus rigidity. In particular, vimentin intermediate filaments undergo phosphorylation and reorientation in smooth muscle cells, which may regulate cell contraction and focal adhesion assembly/disassembly. Motile cells are characterized by a front-rear polarization of the microtubule framework, which regulates all essential processes leading to cell migration through its role in cell mechanics, intracellular trafficking, and signaling. This review recapitulates our current knowledge how the three cytoskeletal systems spatially and temporally modulate the migratory properties of cells. We also summarize the potential role of migration-associated biomolecules in lung and vascular diseases.

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Role of myosin light chain kinase in cardiotrophin-1-induced cardiac myofibroblast cell migration

Abstract: LV, Dixon IM. Role of myosin light chain kinase in cardiotrophin-1-induced cardiac myofibroblast cell migration.

Cited by 28 publications

References 62 publications

Fibroblasts in myocardial infarction: A role in inflammation and repair

Fibroblasts in myocardial infarction: A role in inflammation and repair

The Role of Calmodulin in Tumor Cell Migration, Invasiveness, and Metastasis

The roles and regulation of the actin cytoskeleton, intermediate filaments and microtubules in smooth muscle cell migration

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