KFO 192:  Skeletal Muscle Growth Regulation and Dysregulation

• Subject Area: Medicine ; Biology
• Term: from 2007 to 2015
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 34181657

Alteration in the size and functional capacity of skeletal muscle is a hallmark symptom of muscular dystrophy. However, the process also occurs in common acquired skeletal muscle disorders, such as the cachexia of chronic illnesses. The regulatory mechanisms are largely unknown. Disuse could be involved, although hibernating animals conserve their muscle size and strength despite disuse.
In eight projects, five basic science, three clinically oriented, we study various aspects of skeletal muscle growth: Myostatin (a TGF-beta-superfamily protein) is a negative regulator of muscle mass. Whether inhibition of myostatin is suitable to improve dysferlin-deficient muscular dystrophy (project 6, S. Spuler) or tumour growth in the malignant rhabodmyoscarcoma (project 7, M. Schülke) is subject of animal and cell biological studies. The transport of SMAD, signal transductors of the myostatin pathway across the nuclear lamina will be investigated in project 4 by U. Vinkemeier. The roles of titin (project 1, M. Gotthardt, N. Hübner) and ahnak (project 8, I. Morano, H. Haase) in the development of muscle atrophy will be defined using several knockout mice.
There is evidence that insulin resistance and inflammation are crucial in the development of heart failure associated cachexia (project 2, W. Döhner, S. Anker) and of the devastating critical illness myopathy (project 3, S. Weber-Carstens, J. Spranger). In these disorders as well as in a monogenic model of muscle hypertrophy, LMNA - associated familial partial lipodystrophy Dunnigan (project 9, J. Jordan, M. Boschmann), muscle metabolism will be assessed by microdialysis. We present a unique interdisciplinary programme that includes molecular and cell biologists, neurologists, internists, critical care specialists and clinical pharmacologists. We believe that this Clinical Research Unit brings together scientists and clinician/scientists who seldom communicate with one-another.

• DFG Programme: Clinical Research Units

Projects

• Analysis of nucleocytoplasmic transport in muscle disorders caused by mutations in lamins A/C (Applicant Vinkemeier, Uwe )
• Caveolopathies - insulin resistance, lipid metablism (Applicant Boschmann, Michael )
• Critical illness myopathy and timely electrical muscle stimulation (Applicant Weber-Carstens, Steffen )
• Dynamics of muscle caveolae (Applicant Schülke-Gerstenfeld, Markus )
• Effects of negative energy balance on muscle mass regulation (Applicant Spranger, Joachim )
• Met receptor signaling in muscle growth and repair (Applicant Birchmeier, Carmen )
• Muscle and fat tissue wasting in patients with chronic heart failure: the impact of impaired insulin sensitivity (Applicant Döhner, Ph.D., Wolfram )
• Myostatin in normal and diseased muscle (Applicant Spuler, Simone )
• Regulation of heart failure induced skeletal muscle wasting by protein kinase D1 (Applicant Fielitz, Jens )
• The functional role of ahnak in skeletal muscle fibers in an ahnak knock-out-mouse model (Applicant Morano, Ingo )
• The role of caveolae in statin-induced myopathy (Applicant Steinhagen-Thiessen, Elisabeth )
• Titin-based mechanotransduction in skeletal muscle atrophy and hypertrophy (Applicant Gotthardt, Michael )
• Zentralprojekt 1 (Applicant Spuler, Simone )

• Spokesperson: Professor Dr. Friedrich C. Luft
• Leader: Professorin Dr. Simone Spuler