| 1. |
- Rullman, Eric
(författare)
-
Skeletal muscle matrix metalloproteinase and exercise in humans
- 2011
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Skeletal muscle is a highly plastic tissue; it has a great capacity to adapt to environmental demands throughout life. The structural and functional changes that occur in response to exercise training are well characterized whereas much less is known about these adaptive processes at the cellular and molecular levels. A possibly underestimated aspect of skeletal muscle adaptation to exercise is the remodeling of the extracellular matrix (ECM). Degradation and processing of the extracellular matrix are carried out by a specific category of proteases, especially the matrix metalloproteinase family (MMPs). Such remodeling is of crucial importance for successful extravasation of circulating cells and for the migration of cells between the compartments of the tissue. Furthermore, degradation products of ECM components are not always mere debris; several fragments of structural proteins have biological activity after proteolytic processing, and MMP activity may also release growth factors stored in the ECM. Little is known about these enzymes in skeletal muscle of humans and how physiological stimuli such as exercise and exercise training affect their expression and activity. Therefore, the aim of this thesis was to characterize: 1. skeletal muscle MMP activation in response to a single bout of exercise and exercise training with regard to gene expression and enzyme activity, 2. exchange of factors associated with MMP activity between exercising leg and the circulation during exercise, 3. possible cellular sources of MMP in skeletal muscle tissue and blood, 4. the effects of restricted leg blood flow, and thereby reduced oxygen delivery, to the exercising leg on skeletal muscle and circulating levels of MMP and 5. the effects of the myokine interleukin-6 on MMP levels in skeletal muscle and in the circulation. MMP-9 is activated and transcriptionally upregulated in human skeletal muscle after a single bout of exercise. In contrast, MMP-2 is activated and transcriptionally upregulated in human skeletal muscle by exercise training but not after a single bout of exercise. Factors possibly linked to proteolytic processing of MMP-9, such as collagen IV and VEGF-A, are released from the leg to the circulation during a single bout of exercise in humans. Circulating levels of MMP-9 increase during and after a single bout of exercise in humans but do not seem to originate from the skeletal muscle. The myokine interleukin-6 induces an increase in circulating MMP-9 in parity with what is seen after a single bout of exercise in humans, interleukin-6 also induces gene- expression and release of MMP-9 from the human moncyte cell-line THP-1, but not from human myoblasts, myotubes or endothelial cells indicating that monocytes could be the source of the interleukin-6 induced increase in circulating MMP-9. The results from this thesis show that both MMP-2 and MMP-9 are expressed in skeletal muscle and upregulated by a physiological stimulus such as exercise but probably through different mechanisms. Furthermore, it indicates that remodeling of extracellular matrix and release of growth factors in the skeletal muscle occur after only a few minutes of exercise. Overall, the results support MMPs to play a role in the adaptation of the skeletal muscle to physical activity in humans.
|
|
| 2. |
- Strömberg, Anna, et al.
(författare)
-
Bone marrow derived cells in adult skeletal muscle tissue in humans
- 2013
-
Ingår i: Skeletal Muscle. - : Springer Science and Business Media LLC. - 2044-5040. ; 3:1, s. 12-
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND:During the past decade, several animal studies have demonstrated that in addition to local cells, cells from the bone marrow (BM) possess the ability to contribute to regeneration of injured skeletal muscle tissue. In addition, in mice, regular physical activity has been displayed to be a sufficient stimulus for BM-derived cell contribution to the muscle, indicating that this is part of the ongoing physiological remodeling of skeletal muscle. However, whether BM-derived cells participate in human skeletal muscle remodeling is not known. To this end, we analyzed the incorporation of BM-derived cells in healthy human skeletal muscle in women transplanted with male BM.METHODS:Skeletal muscle biopsies were obtained from the m. vastus lateralis of women transplanted with male donor hematopoietic stem cells 6 to 12 years earlier. Healthy women served as controls. Immunohistochemical staining for skeletal muscle fibers, satellite cells (SCs) or endothelial cells (ECs) combined with fluorescent in situ hybridization (FISH) of X and Y chromosomes was used to identify cells of BM origin within the biopsies. Three dimensional confocal imaging was performed to demonstrate colocalization of Y chromosome and DAPI within muscle fibers. To further investigate whether BM-derived cells incorporate into the SC niche, myoblasts were extracted from the biopsies from the transplanted women, cultured, and analyzed using XY FISH and immunocytochemistry.RESULTS:Three dimensional confocal imaging indisputably demonstrated colocalization of Y chromosome and DAPI within muscle fibers. Some Y chromosomes were found within centrally located nuclei. No Y chromosomes were detected in CD56+ SCs in the tissue sections nor in the myoblasts cultured from the extracted SCs. Y chromosome+ ECs were found in all sections from the transplanted subjects. No Y chromosomes were found in the skeletal muscle biopsies obtained from healthy control women.CONCLUSIONS:We demonstrate that BM-derived cells contribute to skeletal muscle fibers and ECs. Our results support that BM contribution to skeletal muscle occurs via direct fusion to muscle fibers, and that the contributing cells derive from the hematopoietic lineage. Thus, the present findings encourage further studies of the importance of this process for the physiological adaptation occurring throughout life.
|
|
