Publications
366 results found
Mourkioti F, Kratsios P, Luedde T, et al., 2006, Targeted ablation of IKK2 improves skeletal muscle strength, maintains mass, and promotes regeneration., J Clin Invest, Vol: 116, Pages: 2945-2954, ISSN: 0021-9738
NF-kappaB is a major pleiotropic transcription factor modulating immune, inflammatory, cell survival, and proliferative responses, yet the relevance of NF-kappaB signaling in muscle physiology and disease is less well documented. Here we show that muscle-restricted NF-kappaB inhibition in mice, through targeted deletion of the activating kinase inhibitor of NF-kappaB kinase 2 (IKK2), shifted muscle fiber distribution and improved muscle force. In response to denervation, IKK2 depletion protected against atrophy, maintaining fiber type, size, and strength, increasing protein synthesis, and decreasing protein degradation. IKK2-depleted mice with a muscle-specific transgene expressing a local Igf-1 isoform (mIgf-1) showed enhanced protection against muscle atrophy. In response to muscle damage, IKK2 depletion facilitated skeletal muscle regeneration through enhanced satellite cell activation and reduced fibrosis. Our results establish IKK2/NF-kappaB signaling as an important modulator of muscle homeostasis and suggest a combined role for IKK inhibitors and growth factors in the therapy of muscle diseases.
Rosenthal N, 2006, Conference of the International Society of Differentiation, DIFFERENTIATION, Vol: 74, Pages: 441-441, ISSN: 0301-4681
Rosenthal N, 2006, Enhancing mammalian regeneration, Publisher: BLACKWELL PUBLISHING, Pages: 449-449, ISSN: 0301-4681
Musaro A, Dobrowolny G, Rosenthal N, 2006, The neuroprotective effects of a locally acting IGF-1 isoform, 8th International Symposium on the Neurobiology and Neuroendocrinology of Aging, Publisher: PERGAMON-ELSEVIER SCIENCE LTD, Pages: 76-80, ISSN: 0531-5565
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- Citations: 33
Rosenthal N, 2006, Full regeneration of the mammalian heart, 28th Annual International-Society-for-Heart-Research North American Section Meeting, Publisher: ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD, Pages: 944-944, ISSN: 0022-2828
Rosenthal N, Mourkioti F, Lara-Pezzi E, et al., 2006, NF-κB signalling in muscle regeneration, 31st Congress of the Federation-of-European-Biochemical-Societies (FEBS), Publisher: BLACKWELL PUBLISHING, Pages: 6-7, ISSN: 1742-464X
Musaro A, Rosenthal N, 2006, The critical role of Insulin-like Growth Factor-1 isoforms in the physiopathology of skeletal muscle, CURRENT GENOMICS, Vol: 7, Pages: 19-32, ISSN: 1389-2029
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- Citations: 10
Yacoub M, Suzuki K, Rosenthal N, 2006, The future of regenerative therapy in patients with chronic heart failure., Nat Clin Pract Cardiovasc Med, Vol: 3 Suppl 1, Pages: S133-S135, ISSN: 1743-4297
Regenerative therapy is a rapidly growing branch of science and medicine, which could have an important impact on the treatment of heart failure, a major cause of disability and death. Regeneration of the damaged myocardium in heart failure can be achieved through different strategies aimed at 'reviving' existing malfunctioning cells, repopulating the myocardium by new cells from exogenous or endogenous sources, altering the extracellular matrix, or increasing blood supply by enhancing vasculogenesis. To date, the clinical application of some of these strategies has had minimal or no impact on the global epidemic of chronic heart failure. However, several small clinical trials have reported varying degrees of functional improvement which could be considerable in some cases. We here review recent progress in the field, suggest an integrated approach, and outline the many gaps in our knowledge which need to be resolved by intensive laboratory research if regenerative therapy for chronic heart failure is to achieve its future potential.
Lara-Pezzi E, Paul AC, McCullagh K, et al., 2006, Calcineurin isoforms in striated muscle regeneration, Annual Autumn Meeting of the British-Society-for-Cardiovascular-Research, Publisher: B M J PUBLISHING GROUP, ISSN: 1355-6037
Santini MP, Winn N, Rosenthal N, 2006, Signalling pathways in cardiac regeneration., Pages: 228-238, ISSN: 1528-2511
Regeneration is a homeostatic mechanism evolved to maintain or restore the original architecture of a damaged tissue by recapitulating part of its original embryonic development. Our focus has been to intervene in signalling mechanisms at work in the regeneration process to increase the efficiency of mammalian tissue repair. In response to traumatic injury, both skeletal and cardiac muscle activate signalling cascades involved in inflammation, cell death and fibrosis, often at the expense of cell survival and regeneration. In contrast, mice expressing a local isoform of insulin-like growth factor 1 (mIGF1) as a muscle-specific transgene maintain skeletal muscle integrity and ageing, counter muscle decline in degenerative muscle disease, and show enhanced stem cell homing to damaged muscle. Under the control of a cardiac-specific promoter, the mIGF1 transgene directs efficient repair of infarcted heart tissue without scar formation. In both models, novel signalling pathways are employed, suggesting specific mechanisms through which mIGF1 improves regeneration and providing potential targets for clinical intervention.
Musaró A, Giacinti C, Dobrowolny G, et al., 2006, Role of mIGF-1 on muscle regeneration and neuromuscular disease, International Workshop on Regenerative Medicine, Publisher: COGNIZANT COMMUNICATION CORP, Pages: S128-S128, ISSN: 0963-6897
Mourkiouti F, Kratsios P, Luedde T, et al., 2006, Targeted ablation of IKK2 improves skeletal muscle strength, maintains mass and promotes regeneration, J Clin Invest, Vol: 116, Pages: 2945-2954
Rosenthal N, Santini MP, Musarò A, 2006, Growth factor enhancement of cardiac regeneration, International Workshop on Regenerative Medicine, Publisher: COGNIZANT COMMUNICATION CORP, Pages: S41-S45, ISSN: 0963-6897
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- Citations: 6
Rosenthal N, 2005, Prologue, Success Strategies for Women in Science: A Portable Mentor, Pages: xxvii-xxx
Rosenthal N, 2005, Growth factor enhancement of mammalian regeneration, Meeting on Stem Cell and Regeneration of the Kidney, Publisher: BLACKWELL PUBLISHING, Pages: 1965-1966, ISSN: 0085-2538
Mourkioti F, Rosenthal N, 2005, IGF-1, inflammation and stem cells: interactions during muscle regeneration, TRENDS IN IMMUNOLOGY, Vol: 26, Pages: 535-542, ISSN: 1471-4906
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- Citations: 197
Schulze PC, Fang J, Kassik KA, et al., 2005, Transgenic overexpression of locally acting insulin-like growth factor-1 inhibits ubiquitin-mediated muscle atrophy in chronic left-ventricular dysfunction, CIRCULATION RESEARCH, Vol: 97, Pages: 418-426, ISSN: 0009-7330
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- Citations: 100
Scicchitano BM, Spath L, Musarò A, et al., 2005, Vasopressin-dependent myogenic cell differentiation is mediated by both Ca<SUP>2+</SUP>/calmodulin-dependent kinase and calcineurin pathways, MOLECULAR BIOLOGY OF THE CELL, Vol: 16, Pages: 3632-3641, ISSN: 1059-1524
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- Citations: 36
Freitas-Matos TG, Sampaio AC, Vasconcelos M, et al., 2005, A complex nuclear receptor response element controls atrial specificity of the SMyHC3 promoter in mice., 64th Annual Meeting of the Society-for-Development-Biology, Publisher: ACADEMIC PRESS INC ELSEVIER SCIENCE, Pages: 675-675, ISSN: 0012-1606
Rosenthal N, 2005, Youthful prospects for human stem-cell therapy - In another few decades, revised attitudes towards stem cells could lead to disease prevention and life extension, EMBO REPORTS, Vol: 6, Pages: S30-S34, ISSN: 1469-221X
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- Citations: 8
Song YH, Li YX, Du J, et al., 2005, Angiotensin II, insulin-like growth factor-1 and heart failure, 27th Annual Meeting of the American Section of the International-Society-of-Heart-Research, Publisher: ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD, Pages: 849-850, ISSN: 0022-2828
Song YH, Godard M, Li YX, et al., 2005, Insulin-like growth factor I-mediated skeletal muscle hypertrophy is characterized by increased mTOR-p70S6K signaling without increased Akt phosphorylation, JOURNAL OF INVESTIGATIVE MEDICINE, Vol: 53, Pages: 135-142, ISSN: 1081-5589
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- Citations: 54
Shavlakadze T, Winn N, Rosenthal N, et al., 2005, Reconciling data from transgenic mice that overexpress IGF-I specifically in skeletal muscle, GROWTH HORMONE & IGF RESEARCH, Vol: 15, Pages: 4-18, ISSN: 1096-6374
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- Citations: 112
Song YH, Li YX, Du J, et al., 2005, Muscle-specific expression of IGF-1 blocks angiotensin II-induced skeletal muscle wasting, JOURNAL OF CLINICAL INVESTIGATION, Vol: 115, Pages: 451-458, ISSN: 0021-9738
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- Citations: 278
Dobrowolny G, Giacinti C, Pelosi L, et al., 2005, Muscle expression of a local Igf-1 isoform protects motor neurons in an ALS mouse model, The Journal of Cell Biology, Vol: 168, Pages: 193-199, ISSN: 0021-9525
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by a selective degeneration of motor neurons, atrophy, and paralysis of skeletal muscle. Although a significant proportion of familial ALS results from a toxic gain of function associated with dominant SOD1 mutations, the etiology of the disease and its specific cellular origins have remained difficult to define. Here, we show that muscle-restricted expression of a localized insulin-like growth factor (Igf) -1 isoform maintained muscle integrity and enhanced satellite cell activity in SOD1G93A transgenic mice, inducing calcineurin-mediated regenerative pathways. Muscle-specific expression of local Igf-1 (mIgf-1) isoform also stabilized neuromuscular junctions, reduced inflammation in the spinal cord, and enhanced motor neuronal survival in SOD1G93A mice, delaying the onset and progression of the disease. These studies establish skeletal muscle as a primary target for the dominant action of inherited SOD1 mutation and suggest that muscle fibers provide appropriate factors, such as mIgf-1, for neuron survival.
Turrini P, Monego G, Gonzalez J, et al., 2005, Human hepatocytes in mice receiving pre-immune injection with human cord blood cells, BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, Vol: 326, Pages: 66-73, ISSN: 0006-291X
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- Citations: 21
The Eumorphia Consortium, 2005, EMPReSS: standardized phenotype screens for functional annotation of the mouse genome, Nat Genet, Vol: 37, Pages: 1155-1156, ISSN: 1061-4036
Shavlakadze T, White J, Hoh JFY, et al., 2004, Targeted expression of insulin-like growth factor-1 reduces early myofiber necrosis in dystrophic mdx mice, MOLECULAR THERAPY, Vol: 10, Pages: 829-843, ISSN: 1525-0016
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- Citations: 89
Schulze PC, Fang J, Kassik KA, et al., 2004, Transgenic overexpression of mIGF-1 increases skeletal muscle phosphorylation of FOXO forkhead transcription factors and blocks expression of the ubiquitin ligase atrogin-1 in chronic ventricular dysfunction, 77th Scientific Meeting of the American-Heart-Association, Publisher: LIPPINCOTT WILLIAMS & WILKINS, Pages: 45-45, ISSN: 0009-7322
Rosenthal N, Santini MP, 2004, Stem Cells and the Regenerating Heart, Handbook of Stem Cells, Pages: 449-454, ISBN: 9780124366435
In response to functional stress, the heart can increase its muscle mass through cellular hypertrophy, but a damaged heart needs a rapid response to repair damage to the muscle wall and maintain adequate blood flow to the rest of the body. In contrast to the mammalian skeletal muscle that regenerates injured tissue through activation of quiescent myogenic precursor or multipotent adult stem cell populations, the heart does not appear to retain equivalent reserve cell populations to promote myofiber repair. The relative scarcity of progenitor cells residing in the adult myocardium has prompted a search for a renewable source of circulating somatic progenitor cells that might home to the heart in response to damage. The capacity of the heart to regenerate may not be a common attribute shared by all cardiomyocytes. Although longitudinal analyses of single cultured new cardiomyocytes revealed that many cells enter into S phase in response to serum-activated pathways dependent on the phosphorylation of the Rb protein, the majority of these cells stablely arrest at either entry to mitosis or during cytokinesis. After surgical removal of the ventricular apex and rapid clotting at the site of amputation, proliferating cardiac myofibers replace the clot and regenerate missing tissue, with minimal scarring. The requirement for cell cycle reentry in this model is supported by the decreased regeneration and increased fibrosis in a temperature-sensitive mutant of a mitotic checkpoint kinase, mps. It is still formally possible that the activation of cardiac progenitor cells is largely responsible for the extraordinary capacity of the adult zebrafish to restore extensive portions of the heart.
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