Periostin Responds to Mechanical Stress and Tension by Activating the MTOR Signaling Pathway

Current knowledge about Periostin biology has expanded from its recognized functions in embryogenesis and bone metabolism to its roles in tissue repair and remodeling and its clinical implications in cancer. Emerging evidence suggests that Periostin plays a critical role in the mechanism of wound healing; however, the paracrine effect of Periostin in epithelial cell biology is still poorly understood. We found that epithelial cells are capable of producing endogenous Periostin that, unlike mesenchymal cell, cannot be secreted. Epithelial cells responded to Periostin paracrine stimuli by enhancing cellular migration and proliferation and by activating the mTOR signaling pathway. Interestingly, biomechanical stimulation of epithelial cells, which simulates tension forces that occur during initial steps of tissue healing, induced Periostin production and mTOR activation. The molecular association of Periostin and mTOR signaling was further dissected by administering rapamycin, a selective pharmacological inhibitor of mTOR, and by disruption of Raptor and Rictor scaffold proteins implicated in the regulation of mTORC1 and mTORC2 complex assembly. Both strategies resulted in ablation of Periostin-induced mitogenic and migratory activity. These results indicate that Periostin-induced epithelial migration and proliferation requires mTOR signaling. Collectively, our findings identify Periostin as a mechanical stress responsive molecule that is primarily secreted by fibroblasts during wound healing and expressed endogenously in epithelial cells resulting in the control of cellular physiology through a mechanism mediated by the mTOR signaling cascade.This work was funded by the National Institutes of Health (NIH/NCI) P50-CA97248 (University of Michigan Head and Neck SPORE)

Genetic variation and exercise-induced muscle damage: implications for athletic performance, injury and ageing.

Prolonged unaccustomed exercise involving muscle lengthening (eccentric) actions can result in ultrastructural muscle disruption, impaired excitation-contraction coupling, inflammation and muscle protein degradation. This process is associated with delayed onset muscle soreness and is referred to as exercise-induced muscle damage. Although a certain amount of muscle damage may be necessary for adaptation to occur, excessive damage or inadequate recovery from exercise-induced muscle damage can increase injury risk, particularly in older individuals, who experience more damage and require longer to recover from muscle damaging exercise than younger adults. Furthermore, it is apparent that inter-individual variation exists in the response to exercise-induced muscle damage, and there is evidence that genetic variability may play a key role. Although this area of research is in its infancy, certain gene variations, or polymorphisms have been associated with exercise-induced muscle damage (i.e. individuals with certain genotypes experience greater muscle damage, and require longer recovery, following strenuous exercise). These polymorphisms include ACTN3 (R577X, rs1815739), TNF (-308 G>A, rs1800629), IL6 (-174 G>C, rs1800795), and IGF2 (ApaI, 17200 G>A, rs680). Knowing how someone is likely to respond to a particular type of exercise could help coaches/practitioners individualise the exercise training of their athletes/patients, thus maximising recovery and adaptation, while reducing overload-associated injury risk. The purpose of this review is to provide a critical analysis of the literature concerning gene polymorphisms associated with exercise-induced muscle damage, both in young and older individuals, and to highlight the potential mechanisms underpinning these associations, thus providing a better understanding of exercise-induced muscle damage

Natação e aspectos morfológicos do músculo esquelético em processo de reparo após criolesão Swimming and morphology of skeletal muscle repair process after cryoinjury

O objetivo do estudo foi investigar a influência da natação sobre as alterações morfológicas do músculo esquelético em processo de reparo após criolesão. Foram usados 45 ratos divididos em cinco grupos: controle (n=5); sham (n=5), adaptação (n=5), criolesionados e tratados com natação sacrificados após 7, 14 e 21 dias (n=15); criolesionados e sem tratamento aquático sacrificados após 7, 14 e 21 dias (n=15). As sessões de natação foram realizadas 6 vezes por semana com 90 min de duração cada. Ao término do protocolo os animais foram sacrificados e a análise morfológica da área da lesão foi realizada. A análise morfológica semiquantitativa demonstrou que os músculos do grupo controle apresentaram aspecto histológico normal. O grupo sham apresentou edema, mionecrose e infiltrado inflamatório em grau 1. Nos grupos 7, 14 e 21 dias, não existiram diferenças estatisticamente significativas nas 4 etapas de remodelamento tecidual avaliadas (infiltrado inflamatório, edema, necrose e fibras musculares imaturas) entre os grupos lesionados quando comparados aos grupos com lesão e tratamento aquático. Em conclusão, foi possível verificar que a natação não causou alterações morfológicas durante o reparo do músculo esquelético após criolesão.<br>The aim of study was investigate the influence of swimming on the morphological changes in skeletal muscle repair process following cryoinjury. There were used 45 rats divided into 5 groups: control (n=5), sham (n=5), adaptation (n=5), cryolesioned treated with swimming and sacrificed after 7, 14 and 21 days (n=15), untreated and cryolesioned sacrificed after 7, 14, and 21 days (n=15). Animals swan for 90 min/ each session and 6 times a week. At the end of the protocol, the animals were sacrificed and morphological analysis of the lesion area was performed. The semi-quantitative morphological analysis showed that the muscles in the control group exhibited normal histological aspects while the sham group exhibited edema, myonecrosis and inflammatory infiltrate grade 1. In groups 7, 14, and 21 days, the results indicated that there were no statistically significant differences in four stages of tissue remodeling evaluated (inflammatory infiltration, edema, necrosis, and immature muscle fibers) between the injured groups compared to groups with lesion and treated with swimming. In conclusion, it was verified that swimming did not alter morphological aspects of skeletal muscle during the repair process following cryoinjury

Flower differentiation of azalea depends on genotype and not on the use of plant growth regulators

Flowering is a complex process which starts with the induction and development of the flower buds. For azalea (Rhododendron simsii hybrids), flower induction was hastened by the application of chlormequat and took place within 11 days after treatment. Subsequent flower bud differentiation was not altered by the application rate of the plant growth regulators (PGR) chlormequat and paclobutrazol, nor by temperature or light sum. There were however, large genotypic variations in flower bud differentiation rate. For all cultivars a linear phase until flower primordia were fully differentiated and the style started to enlarge (flower bud stage 7), was followed by a slower final development (to stage 8). The linear phase was fastest for the semi-early flowering cultivars (‘Mont Blanc’, ‘M. Marie’ and ‘Otto’), requiring only 46 or 48 days to reach flower bud stage 7 after the first PGR treatment. Two late flowering cultivars (‘Thesla’ and ‘Sachsenstern’) had the slowest differentiation, requiring 64 days to reach stage 7. The early flowering cultivars (‘H. Vogel’ sports) and two late flowering cultivars (‘Mw. G. Kint’ and ‘Tamira’) required 54 and 52 days, respectively, after the first PGR treatment to reach stage 7. To reach flower bud stage 8, a similar trend in velocity was seen, the semi-early flowering cultivars requiring the least amount of days (17 to 18 days), the late flowering cultivars ‘Thesla’ and ‘Sachsenstern’ requiring the highest amount of days (24) and the early flowering cultivars and the late flowering cultivars ‘Mw. G. Kint’ and ‘Tamira’ requiring an intermediate number of days (20 to 22 days)