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- Põlajeva, Jelena, 1983-, et al.
(författare)
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miRNA-21 is developmentally regulated in mouse brain and is co-expressed with SOX2 in glioma
- 2012
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Ingår i: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 12, s. 378-
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundMicroRNAs (miRNAs) and their role during tumor development have been studied in greatdetail during the last decade, albeit their expression pattern and regulation during normaldevelopment are however not so well established. Previous studies have shown that miRNAsare differentially expressed in solid human tumors. Platelet-derived growth factor (PDGF)signaling is known to be involved in normal development of the brain as well as in malignantprimary brain tumors, gliomas, but the complete mechanism is still lacking. We decided toinvestigate the expression of the oncogenic miR-21 during normal mouse development andglioma, focusing on PDGF signaling as a potential regulator of miR-21.MethodsWe generated mouse glioma using the RCAS/tv-a system for driving PDGF-BB expression ina cell-specific manner. Expression of miR-21 in mouse cell cultures and mouse brain wereassessed using Northern blot analysis and in situ hybridization. Immunohistochemistry andWestern blot analysis were used to investigate SOX2 expression. LNA-modified siRNA wasused for irreversible depletion of miR-21. For inhibition of PDGF signaling Gleevec(imatinib mesylate), Rapamycin and U0126, as well as siRNA were used. Statisticalsignificance was calculated using double-sided unpaired Student´s t-test.ResultsWe identified miR-21 to be highly expressed during embryonic and newborn braindevelopment followed by a gradual decrease until undetectable at postnatal day 7 (P7), thiscorrelated with SOX2 expression. Furthermore, miR-21 and SOX2 showed up-regulation andoverlapping expression pattern in RCAS/tv-a generated mouse brain tumor specimens. Uponirreversible depletion of miR-21 the expression of SOX2 was strongly diminished in bothmouse primary glioma cultures and human glioma cell lines. Interestingly, in normalfibroblasts the expression of miR-21 was induced by PDGF-BB, and inhibition of PDGFsignaling in mouse glioma primary cultures resulted in suppression of miR-21 suggesting thatmiR-21 is indeed regulated by PDGF signaling.ConclusionsOur data show that miR-21 and SOX2 are tightly regulated already during embryogenesisand define a distinct population with putative tumor cell of origin characteristics. We believethat miR-21 is a mediator of PDGF-driven brain tumors, which suggests miR-21 as apromising target for treatment of glioma.
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| 2. |
- Nilsson, Johnny, et al.
(författare)
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Kinematic, kinetic and electromyographic adaptation to speed and resistance in double poling cross country skiing
- 2013
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Ingår i: European Journal of Applied Physiology. - : Springer Science and Business Media LLC. - 1439-6319 .- 1439-6327. ; 113:6, s. 1385-1394
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Tidskriftsartikel (refereegranskat)abstract
- This study incorporated variations in speed and the horizontal resistance acting upon elite female skiers during double poling (DP) on a treadmill and specifically analyzed biomechanical adaptations to these variations. Whole body kinematics and pole force data were recorded and used to calculate the moment of force acting on the shoulder and elbow joints. Data were obtained with a 3D optoelectronic system using reflective markers at given anatomical landmarks. Forces along the long axis of the right pole were measured with a piezoelectric force transducer. Surface electrodes were used to record EMG activity in the rectus femoris, rectus abdominis, latissimus dorsi and triceps brachii muscles. In a first set of recordings, the participants double poled with zero elevation at five different speeds from 8 to 17 km h(-1). In a second set of recordings, horizontal resistance was added by weights (0.4-1.9 kg) attached to a pulley system pulling the skier posteriorly during DP at 14 km h(-1). Results showed increasing relative duration of the thrust phase with increasing resistance, but not with speed. Significant kinematic differences occurred with increase in both speed and resistance. The mean (+/- SD) horizontal force components ranged between 1.7 (+/- 1.3) and 2.8 (+/- 1.1) percent (%) bodyweight (BW) in the speed adaptation and 3.1 (+/- 0.6) and 4.0 (+/- 1.3) % BW in the adaptation to horizontal resistance. Peak muscle activity showed a central to peripheral (proximo-distal) activation sequence. The temporal cycle phase pattern in the adaptation to speed and horizontal resistance differed.
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