Collagen loss and impaired wound healing is associated with c‐Myb deficiency

Kopecki, Zlatko; Luchetti, Michele Maria; Adams, Damian; Strudwick, Xanthe L.; Mantamadiotis, Theo; Stoppacciaro, Antonella; Gabrielli, Armando; Ramsay, Robert G.; Cowin, Allison J.

doi:10.1002/path.2113

Cited by 62 publications

(54 citation statements)

References 24 publications

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“…The skin of heterozygous c-Myb-deficient mice exhibits impaired wound-repair capability and reduced collagen type I levels. C-Myb-deficient wounds show reduced fibroblast cell proliferation and collagen levels, but the TGF-β1 expression levels are elevated [48]. Ma HH et al have reported that the antisense RNA of c-Myb suppressed collagen I-a1 expression in cultured hepatic stellate cells [49].…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-150 Inhibits the Activation of Cardiac Fibroblasts by Regulating c-Myb

Deng

Chen

Liu

et al. 2016

Cell Physiol Biochem

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Background/Aims: Cardiac fibrosis is the primary cause of deteriorated cardiac function in various cardiovascular diseases. Numerous studies have demonstrated that microRNAs (miRNAs) are critical regulators of myocardial fibrosis. Specifically, many studies have reported that miR-150 is downregulated in cardiovascular diseases, such as acute myocardial infarction (AMI), myocardial hypertrophy and myocardial fibrosis. However, the exact role of miR-150 in these pathological processes remains unknown. Methods: We used the transverse aortic constriction (TAC) mouse model to study the role of miR-150 in cardiac fibrosis induced by pressure overload. After the TAC operation, qRT-PCR was used to measure the expression profiles of miR-150 in left ventricle tissues and populations of primary heart cell types. Then, we used both miR-150 knockout mice and wild type (WT) mice in the TAC model. Changes in cardiac function and pathology were measured using transthoracic echocardiography and pathological analysis, respectively. Furthermore, we predicted the target of miR-150 in cardiac fibroblasts (CFs) and completed in vitro CF transfection experiments using miR-150 analogs and siRNA corresponding to the predicted target. Results: We observed decreased expression levels of miR-150 in hearts suffering pressure overload, and these levels decreased more sharply in CFs than in cardiomyocytes. In addition, the degrees of cardiac function deterioration and cardiac fibrosis in miR-150-/- mice were more severe than were those in WT mice. By transfecting CFs with an miR-150 analog in vitro, we observed that miR-150 inhibited cardiac fibroblast activation. We predicted that the transcription factor c-Myb was the target of miR-150 in CFs. Transfecting CFs with c-Myb siRNA eliminated the effects of an miR-150 inhibitor, which promoted CF activation. Conclusion: These findings reveal that miR-150 acts as a pivotal regulator of pressure overload-induced cardiac fibrosis by regulating c-Myb.

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Section: Discussionmentioning

confidence: 99%

MicroRNA-150 Inhibits the Activation of Cardiac Fibroblasts by Regulating c-Myb

Deng

Chen

Liu

et al. 2016

Cell Physiol Biochem

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“…As mentioned earlier, a role for collagen I in promoting COX-2 expression in gestational breast cancer has been defined [83]. Collagen I (COL1A2) is a target gene of c-Myb [134], thus a c-Myb-Collagen I-COX-2 inductive pathway may serve as an alternative means through which cMyb may indirectly govern the expression of COX-2 in breast cancer. Taken together, these findings lend support to the notion that the c-Myb-COX-2 inductive relationship may extend beyond colorectal cancer.…”

Section: Putative C-myb-cox2 Pathwaymentioning

confidence: 99%

New Insights on COX-2 in Chronic Inflammation Driving Breast Cancer Growth and Metastasis

Hugo

Saunders

Ramsay

et al. 2015

J Mammary Gland Biol Neoplasia

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The medicinal use of aspirin stretches back to ancient times, before it was manufactured in its pure form in the late 19th century. Its accepted mechanistic target, cyclooxygenase (COX), was discovered in the 1970s and since this landmark discovery, the therapeutic application of aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) has increased dramatically. The most significant benefits of NSAIDs are in conditions involving chronic inflammation (CI). Given the recognized role of CI in cancer development, the use of long-term NSAID treatment in the prevention of cancer is an enticing possibility. COX-2 is a key driver of CI, and here we review COX-2 expression as a predictor of survival in various cancer types, including breast. Obesity and post-partum involution are natural inflammatory states that are associated with increased breast cancer risk. We outline the COX-2 mediated mechanisms contributing to the growth of cancers. We dissect the cellular mechanism of epithelial-mesenchymal transition (EMT) and how COX-2 may induce this to facilitate tumor progression. Finally we examine the potential regulation of COX-2 by c-Myb, and the possible interplay between c-Myb/COX-2 in proliferation, and hypoxia inducible factor-1 alpha (HIF1α)/COX-2 in invasive pathways in breast cancer.

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“…Wound-healing and random cell migration assays were performed essentially as described previously (Pankov et al, 2005;Kopecki et al, 2007) by using an AxioCam MRm camera (Carl Zeiss) on an Axiovert 200 automatic microscope equipped with closed heating and CO 2 perfusion devices. Maximal wound closure rates corresponded to normalized slopes of linear equations derived from regression analyses of the area over time plots shown in Figure 11B.…”

Section: Video-and Electron Microscopy and Microinjectionmentioning

confidence: 99%

“…Fluorescent recovery after photobleaching (FRAP) experiments were performed on a dual-headed, confocal microscope (FluoView 1000; Olympus, Hamburg, Germany) with cells cotransfected (overnight) with myc-tagged L61-Rac1 and EGFP-actin or EGFP-p16B at a ratio of 2:1, and analyzed as described previously (Lai et al, 2008). Wound-healing and random cell migration assays were performed essentially as described previously (Pankov et al, 2005;Kopecki et al, 2007) by using an AxioCam MRm camera (Carl Zeiss) on an Axiovert 200 automatic microscope equipped with closed heating and CO 2 perfusion devices. Maximal wound closure rates corresponded to normalized slopes of linear equations derived from regression analyses of the area over time plots shown in Figure 11B.…”

mentioning

confidence: 99%

Cortactin Promotes Migration and Platelet-derived Growth Factor-induced Actin Reorganization by Signaling to Rho-GTPases

Lai

Szczodrak

Oelkers

et al. 2009

MBoC

109

112

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Dynamic actin rearrangements are initiated and maintained by actin filament nucleators, including the Arp2/3-complex. This protein assembly is activated in vitro by distinct nucleation-promoting factors such as Wiskott-Aldrich syndrome protein/Scar family proteins or cortactin, but the relative in vivo functions of each of them remain controversial. Here, we report the conditional genetic disruption of murine cortactin, implicated previously in dynamic actin reorganizations driving lamellipodium protrusion and endocytosis. Unexpectedly, cortactin-deficient cells showed little changes in overall cell morphology and growth. Ultrastructural analyses and live-cell imaging studies revealed unimpaired lamellipodial architecture, Rac-induced protrusion, and actin network turnover, although actin assembly rates in the lamellipodium were modestly increased. In contrast, platelet-derived growth factor-induced actin reorganization and Rac activation were impaired in cortactin null cells. In addition, cortactin deficiency caused reduction of Cdc42 activity and defects in random and directed cell migration. Reduced migration of cortactin null cells could be restored, at least in part, by active Rac and Cdc42 variants. Finally, cortactin removal did not affect the efficiency of receptor-mediated endocytosis. Together, we conclude that cortactin is fully dispensable for Arp2/3-complex activation during lamellipodia protrusion or clathrin pit endocytosis. Furthermore, we propose that cortactin promotes cell migration indirectly, through contributing to activation of selected Rho-GTPases. INTRODUCTIONCell migration is a complex process requiring the coordinated activities of multiple cellular machines, driving actin polymerization, actin-myosin II-based force generation, and coupling to the extracellular matrix. However, the relative contribution of each of these machines to the different steps in the motility cycle is just beginning to emerge. Irrespective of the complexity of coordination of these activities, it is commonly agreed that protrusion at the cell front is initiated by localized actin polymerization, to form structures such as lamellipodia or ruffles (Small et al., 2002;Pollard and Borisy, 2003).The best characterized factors driving the nucleation of actin filaments in vertebrate cells are the Arp2/3-complex and formins (Pollard, 2007). Arp2/3-complex activity is considered essential for processes as diverse as lamellipodium protrusion, actin assembly during clathrin-mediated endocytosis, podosome formation, and different types of hostpathogen interaction (Goley and Welch, 2006;Linder, 2007).Activators of Arp2/3-complex are termed nucleation promoting factors (NPFs) and are roughly subdivided into class I and II composed of classical members Wiskott-Aldrich syndrome protein (WASP)/WASP family Verprolin-homologous protein (WAVE) proteins and cortactin, respectively (Welch and Mullins, 2002). This distinction is derived, at least in part, from their mode of interaction with actin: the WH2 domains of class I and tande...

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Collagen loss and impaired wound healing is associated with c‐Myb deficiency

Cited by 62 publications

References 24 publications

MicroRNA-150 Inhibits the Activation of Cardiac Fibroblasts by Regulating c-Myb

MicroRNA-150 Inhibits the Activation of Cardiac Fibroblasts by Regulating c-Myb

New Insights on COX-2 in Chronic Inflammation Driving Breast Cancer Growth and Metastasis

Cortactin Promotes Migration and Platelet-derived Growth Factor-induced Actin Reorganization by Signaling to Rho-GTPases

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