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Projects / Programmes source: ARIS

Molecular mechanisms of specificity in regulation of secretion and action of muscle-derived cytokines

Research activity

Code Science Field Subfield
3.07.00  Medical sciences  Metabolic and hormonal disorders   
3.01.00  Medical sciences  Microbiology and immunology   

Code Science Field
3.02  Medical and Health Sciences  Clinical medicine 
3.01  Medical and Health Sciences  Basic medicine 
Keywords
Myokines, skeletal muscle, IL-6, pro-inflammatory cytokines, tocilizumab, JAK inhibitors
Evaluation (rules)
source: COBISS
Points
10,155.86
A''
1,969.07
A'
5,191.39
A1/2
7,360.09
CI10
28,324
CImax
2,687
h10
67
A1
36.71
A3
4.25
Data for the last 5 years (citations for the last 10 years) on July 21, 2024; A3 for period 2018-2022
Data for ARIS tenders ( 04.04.2019 – Programme tender, archive )
Database Linked records Citations Pure citations Average pure citations
WoS  941  35,176  31,640  33.62 
Scopus  840  39,121  35,498  42.26 
Researchers (25)
no. Code Name and surname Research area Role Period No. of publicationsNo. of publications
1.  19627  Ksenija Babič Benedik    Technical associate  2021 - 2024 
2.  51203  Blaž Burja  Medical sciences  Technical associate  2021 - 2022  49 
3.  37636  Klemen Dolinar  Medical sciences  Technical associate  2021 - 2024  68 
4.  50628  PhD Katja Fink  Medical sciences  Researcher  2022 - 2024  29 
5.  18548  PhD Helena Haque Chowdhury  Neurobiology  Researcher  2021 - 2024  155 
6.  22344  PhD Alojzija Hočevar  Microbiology and immunology  Researcher  2021 - 2024  406 
7.  27585  PhD Jernej Jorgačevski  Medical sciences  Researcher  2021 - 2024  180 
8.  39765  Monika Krošel  Microbiology and immunology  Technical associate  2023 - 2024  22 
9.  56517  Marko Kurnik  Cardiovascular system  Researcher  2023 
10.  28845  PhD Katja Lakota  Microbiology and immunology  Researcher  2021 - 2024  247 
11.  16345  PhD Tomaž Marš  Neurobiology  Researcher  2021 - 2024  345 
12.  52604  Miha Mežnar  Cardiovascular system  Researcher  2021 - 2022 
13.  19318  PhD Katarina Miš  Neurobiology  Researcher  2021 - 2024  194 
14.  21397  PhD Helena Motaln  Biochemistry and molecular biology  Researcher  2021 - 2024  208 
15.  38271  PhD Manca Ogrič  Microbiology and immunology  Technical associate  2023 - 2024  48 
16.  20735  PhD Roman Parežnik  Neurobiology  Researcher  2021 - 2024  113 
17.  29467  PhD Katja Perdan Pirkmajer  Microbiology and immunology  Researcher  2021 - 2024  163 
18.  28351  PhD Sergej Pirkmajer  Neurobiology  Head  2021 - 2024  466 
19.  21806  PhD Matej Podbregar  Cardiovascular system  Researcher  2021 - 2024  333 
20.  15813  PhD Boris Rogelj  Neurobiology  Researcher  2021 - 2024  412 
21.  30545  PhD Žiga Rotar  Microbiology and immunology  Researcher  2021 - 2024  317 
22.  38850  PhD Nives Škorja Milić  Neurobiology  Researcher  2023 - 2024  18 
23.  13601  PhD Matija Tomšič  Microbiology and immunology  Researcher  2021 - 2024  767 
24.  20214  PhD Nina Vardjan  Neurobiology  Researcher  2021 - 2024  269 
25.  03702  PhD Robert Zorec  Neurobiology  Researcher  2021 - 2024  803 
Organisations (4)
no. Code Research organisation City Registration number No. of publicationsNo. of publications
1.  0381  University of Ljubljana, Faculty of Medicine  Ljubljana  1627066  48,743 
2.  0106  Jožef Stefan Institute  Ljubljana  5051606000  91,961 
3.  0312  University Medical Centre Ljubljana  Ljubljana  5057272000  77,953 
4.  1187  General hospital Celje  Celje  5064716  2,832 
Abstract
Title: Molecular mechanisms of specificity in regulation of secretion and action of muscle-derived cytokines Acronym: MyoCRINE Background: Physical activity is one of the most effective measures against chronic non-communicable diseases (NCDs), including obesity, type 2 diabetes, cardiovascular diseases, some types of cancer, and neuropsychiatric disorders. Secretion of interleukin-6 (IL-6) and other myokines from contracting skeletal muscle is thought to represent a major mechanism by which exercise protects against these diseases. Myokine signalling could therefore be exploited for pharmacological treatment of these diseases. Unfortunately, clinically useful myokine-based therapies have not emerged. In contrast, therapies that block the action of IL-6, a prototypical myokine and the founding member of the myokine family, have had great clinical success in rheumatology. Thus, there seems to be a major gap in our understanding of beneficial effects of IL-6 as a myokine. Problem identification: Increase in IL-6 secretion from contracting skeletal muscles during exercise suppresses inflammation and improves metabolic homeostasis. In contrast, increased IL-6 secretion from immune cells and adipose tissue, which occurs in chronic inflammatory rheumatic diseases, obesity, physical inactivity, as well as ageing, promotes inflammation and leads to metabolic dysregulation. Mechanisms which determine whether IL-6 opposes or promotes inflammatory processes and impairment of metabolic regulation have not been explained. Hypotheses: To explain the opposing actions of IL-6 and overcome the gaps in current explanations, we formulated three hypotheses: 1) Contractions and other stimuli lead to secretion of distinct intracellular pools of IL-6; 2) Muscle- and stimulus-specific posttranslational modifications modulate actions of IL-6; 3) IL-6 has alternative (non-canonical) IL-6 receptor(s). Objectives of the project: The overarching objective of the MyoCRINE project is to reconcile the contradictory and opposing actions of muscle-derived IL-6 (a myokine) vs. IL-6 that is derived from other sources (not a myokine). Specific objectives of the project are: 1) To explore whether and how contractions regulate specific intracellular pools of IL-6; 2) To investigate regulation and biological roles of posttranslational modifications of IL-6, 3) To investigate the role of non-canonical IL-6 receptors. Implementation: The objectives of the MyoCRINE project will be met by an interdisciplinary team of basic biomedical researchers from Faculty of Medicine (University of Ljubljana) and Jozef Stefan Institute in collaboration with researchers and clinicians from Department of Rheumatology (University Medical Centre Ljubljana) and Intensive Care Unit (General and Teaching Hospital Celje). The interdisciplinary team will carry out state-of-the-art research using advanced techniques and models, such as in vitro innervated contracting human skeletal muscle cells, advanced quantitative fluorescence microscopy with confocal and super-resolution microscopy STED and SIM, proximity-dependent biotin identification (BioID), as well as standard techniques of molecular biology. Collaboration with clinical specialist in rheumatology and intensive care will enable analysis of clinical data and samples, thus increasing the likelihood of translation from bench to bedside. Significance: The MyoCRINE project is expected to make significant new contributions to the field of IL-6 and myokine biology as regards molecular mechanisms of varied and contradictory biological actions of IL-6. Investigation of posttranslational modifications of IL-6 may contribute to development of new diagnostic tests that detect IL-6 molecules with different tissue sources or biological actions. Further, if alternative IL-6 receptor exists, it could represent a novel pharmacological target.
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