Rear Polarization of the Microtubule-Organizing Center in Neointimal Smooth Muscle Cells Depends on PKCα, ARPC5, and RHAMM

Silverman-Gavrila, Rosalind V.; Silverman‐Gavrila, Lorelei B.; Hou, Guangpei; Zhang, Ming; Charlton, Milton P.; Bendeck, Michelle P.

doi:10.1016/j.ajpath.2010.10.001

Cited by 28 publications

(41 citation statements)

References 51 publications

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“…The procedure was performed as described. 41 The truncation point of the common to external and internal carotid arteries was located and isolated, and the common and internal branches were clamped. The external branch was sutured as distal to the truncation as possible, and a Fogarty 2F balloon catheter was inserted into an incision made in the external branch and fed through to the common carotid artery.…”

Section: Methodsmentioning

confidence: 99%

Imaging of Homeostatic, Neoplastic, and Injured Tissues by HA-Based Probes

Veiseh

Breadner

et al. 2011

Biomacromolecules

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An increase in hyaluronan (HA) synthesis, cellular uptake, and metabolism occurs during the remodeling of tissue microenvironments following injury and during disease processes such as cancer. We hypothesized that multimodality HA-based probes selectively target and detectably accumulate at sites of high HA metabolism, thus providing a flexible imaging strategy for monitoring disease and repair processes. Kinetic analyses confirmed favorable available serum levels of the probe following intravenous (i.v.) or subcutaneous (s.c.) injection. Nuclear (technetium-HA, 99mTc-HA, and iodine-HA, 125I-HA), optical (fluorescent Texas Red-HA, TR-HA), and magnetic resonance (gadolinium-HA, Gd-HA) probes imaged liver (99mTc-HA), breast cancer cells/xenografts (TR-HA, Gd-HA), and vascular injury (125I-HA, TR-HA). Targeting of HA probes to these sites appeared to result from selective HA receptor-dependent localization. Our results suggest that HA-based probes, which do not require polysaccharide backbone modification to achieve favorable half-life and distribution, can detect elevated HA metabolism in homeostatic, injured, and diseased tissues.

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Section: Methodsmentioning

confidence: 99%

Imaging of Homeostatic, Neoplastic, and Injured Tissues by HA-Based Probes

Veiseh

Breadner

et al. 2011

Biomacromolecules

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“…More recently, the role of RHAMM was studied following vessel damage using RHAMM−/− mice [57, 119, 181, 197]. Cell culture studies comparing RHAMM−/− and wild type smooth muscle cells and blocking RHAMM function with antibodies show that RHAMM:HA interactions mediate smooth muscle cell adhesion and contraction of collagen gels.…”

Section: Rhamm and Tissue Remodellingmentioning

confidence: 99%

Hyaluronan and RHAMM in Wound Repair and the “Cancerization” of Stromal Tissues

Tölg

McCarthy²,

Yazdani

et al. 2014

BioMed Research International

112

144

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Tumors and wounds share many similarities including loss of tissue architecture, cell polarity and cell differentiation, aberrant extracellular matrix (ECM) remodeling (Ballard et al., 2006) increased inflammation, angiogenesis, and elevated cell migration and proliferation. Whereas these changes are transient in repairing wounds, tumors do not regain tissue architecture but rather their continued progression is fueled in part by loss of normal tissue structure. As a result tumors are often described as wounds that do not heal. The ECM component hyaluronan (HA) and its receptor RHAMM have both been implicated in wound repair and tumor progression. This review highlights the similarities and differences in their roles during these processes and proposes that RHAMM-regulated wound repair functions may contribute to “cancerization” of the tumor microenvironment.

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“…Directed migration of SMCs from the media to the intima and their subsequent proliferation are key causal events in neointimal thickening, but the molecular mechanisms underpinning these events are still not completely understood. Recently we showed that activated SMCs derived from the thickened neointima following an arterial injury exhibit altered patterns of cytoskeletal organization compared with quiescent SMCs derived from the underlying normal medial layers [Silverman‐Gavrila et al, ]. Importantly, the neointimal SMCs migrated with the microtubule organizing center (MTOC) positioned to the rear of the nucleus, and they also exhibited pronounced defects in cell division fidelity including multipolar spindles, centrosome fragmentation, and binucleate cells.…”

Section: Introductionmentioning

confidence: 99%

Spectrin alpha is important for rear polarization of the microtubule organizing center during migration and spindle pole assembly during division of neointimal smooth muscle cells

et al. 2015

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Directed migration of smooth muscle cells (SMCs) from the media to the intima and their subsequent proliferation are key events in atherosclerosis as these cells contribute to the bulk and stability of atheromatous plaques. We showed previously that two cytoskeleton-associated proteins, RHAMM and ARPC5, play important roles in rear polarization of the microtubule organizing centre (MTOC), directed migration, and in maintaining cell division fidelity. These proteins were analyzed to predict additional potential interacting partners using the bioinformatics programs BLAST, ClustalW, and PPI Spider. We identified spectrin alpha, a protein with a known role in actin polymerization as part of the pathway. We show that in migrating SMCs spectrin alpha localizes at the nodes of the actin net, and it partially colocalizes with RHAMM in the perinuclear region. In dividing SMCs spectrin alpha is present at spindle poles and midbody. Moreover, we show that spectrin alpha and RHAMM interact in a complex. Using siRNA to knockdown spectrin disrupted SMC migration, MTOC polarization, and the assembly of a polygonal actin net dorsolateral of the nucleus. Spectrin alpha knockdown also disrupted the organization of the bipolar spindle, chromosome division, and cytokinesis during cell division. The identification of interacting partners such as spectrin alpha and the decoding of pathways involved in polarity regulation during the migration of smooth muscle cells in atherosclerosis is important for identifying atherosclerosis biomarkers and developing therapeutic agents to block atherosclerotic plaque formation.

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Rear Polarization of the Microtubule-Organizing Center in Neointimal Smooth Muscle Cells Depends on PKCα, ARPC5, and RHAMM

Cited by 28 publications

References 51 publications

Imaging of Homeostatic, Neoplastic, and Injured Tissues by HA-Based Probes

Imaging of Homeostatic, Neoplastic, and Injured Tissues by HA-Based Probes

Hyaluronan and RHAMM in Wound Repair and the “Cancerization” of Stromal Tissues

Spectrin alpha is important for rear polarization of the microtubule organizing center during migration and spindle pole assembly during division of neointimal smooth muscle cells

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