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Myoprotective effects of bFGF on skeletal muscle injury in pressure-related deep tissue injury in rats.

ABSTRACT: BACKGROUND:Pressure ulcers (PUs) are a major clinical problem that constitutes a tremendous economic burden on healthcare systems. Deep tissue injury (DTI) is a unique serious type of pressure ulcer that arises in skeletal muscle tissue. DTI arises in part because skeletal muscle tissues are more susceptible than skin to external compression. Unfortunately, few effective therapies are currently available for muscle injury. Basic fibroblast growth factor (bFGF), a potent mitogen and survival factor for various cells, plays a crucial role in the regulation of muscle development and homeostasis. The main purpose of this study was to test whether local administration of bFGF could accelerate muscle regeneration in a rat DTI model. METHODS:Male Sprague Dawley (SD) rats (age 12 weeks) were individually housed in plastic cages and a DTI PU model was induced according to methods described before. Animals were randomly divided into three groups: a normal group, a PU group treated with saline, and a PU group treated with bFGF (10 ?g/0.1 ml) subcutaneously near the wound. RESULTS:We found that application of bFGF accelerated the rate of wound closure and promoted cell proliferation and tissue angiogenesis. In addition, compared to saline administration, bFGF treatment prevented collagen deposition, a measure of fibrosis, and up-regulated the myogenic marker proteins MyHC and myogenin, suggesting bFGF promoted injured muscle regeneration. Moreover, bFGF treatment increased levels of myogenesis-related proteins p-Akt and p-mTOR. CONCLUSIONS:Our findings show that bFGF accelerated injured skeletal muscle regeneration through activation of the PI3K/Akt/mTOR signaling pathway and suggest that administration of bFGF is a potential therapeutic strategy for the treatment of skeletal muscle injury in PUs.

SUBMITTER: Shi H

PROVIDER: S-EPMC4987989 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Myoprotective effects of bFGF on skeletal muscle injury in pressure-related deep tissue injury in rats.

Shi Hongxue H Xie Haohuang H Zhao Yan Y Lin Cai C Cui Feifei F Pan Yingying Y Wang Xiaohui X Zhu Jingjing J Cai Pingtao P Zhang Hongyu H Fu Xiaobing X Xiao Jian J Jiang Liping L

Burns & trauma 20160817

<h4>Background</h4>Pressure ulcers (PUs) are a major clinical problem that constitutes a tremendous economic burden on healthcare systems. Deep tissue injury (DTI) is a unique serious type of pressure ulcer that arises in skeletal muscle tissue. DTI arises in part because skeletal muscle tissues are more susceptible than skin to external compression. Unfortunately, few effective therapies are currently available for muscle injury. Basic fibroblast growth factor (bFGF), a potent mitogen and survi ...[more]

PMID: 27574694

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Project description:The current state-of-the-art diagnosis method for deep tissue injury in muscle, a subcategory of pressure ulcers, is palpation. It is recognized that deep tissue injury is frequently preceded by altered biomechanical properties. A quantitative understanding of the changes in biomechanical properties preceding and during deep tissue injury development is therefore highly desired. In this paper we quantified the spatial-temporal changes in mechanical properties upon damage development and recovery in a rat model of deep tissue injury. Deep tissue injury was induced in nine rats by two hours of sustained deformation of the tibialis anterior muscle. Magnetic resonance elastography (MRE), T2 -weighted, and T2 -mapping measurements were performed before, directly after indentation, and at several timepoints during a 14-day follow-up. The results revealed a local hotspot of elevated shear modulus (from 3.30 ± 0.14 kPa before to 4.22 ± 0.90 kPa after) near the center of deformation at Day 0, whereas the T2 was elevated in a larger area. During recovery there was a clear difference in the time course of the shear modulus and T2 . Whereas T2 showed a gradual normalization towards baseline, the shear modulus dropped below baseline from Day 3 up to Day 10 (from 3.29 ± 0.07 kPa before to 2.68 ± 0.23 kPa at Day 10, P < 0.001), followed by a normalization at Day 14. In conclusion, we found an initial increase in shear modulus directly after two hours of damage-inducing deformation, which was followed by decreased shear modulus from Day 3 up to Day 10, and subsequent normalization. The lower shear modulus originates from the moderate to severe degeneration of the muscle. MRE stiffness values were affected in a smaller area as compared with T2 . Since T2 elevation is related to edema, distributing along the muscle fibers proximally and distally from the injury, we suggest that MRE is more specific than T2 for localization of the actual damaged area.

Project description:Cyclic compressive loading (CCL) is a massage mimetic that improves muscle regrowth from atrophy in adult rats. Therefore, we tested if a single bout of CCL increases anabolic signaling and protein synthesis in muscle during normal, weight-bearing conditions in gastrocnemius muscle from adult and aged rats. Male Brown Norway/F344 rats at 10 (adult) and 30 (aged) months of age were assigned control or CCL (receiving a single bout of CCL). Twenty-four hours following a single bout of CCL there was no change in protein synthesis, Akt, or GSK3? signaling at either age, despite adult rats having higher abundance and activation of mechanosensitive pathways (integrins and integrin-linked kinase). Murf1 was elevated in response to CCL in both age groups, potentially indicating muscle remodeling. Muscle from aged rats exhibited an increase in heat shock protein (HSP) 25 and HSP70 and in the cold shock protein RNA-binding motif 3 (RBM3), demonstrating a unique stress response to CCL in aged muscle only. Finally, muscle from aged rats exhibited higher basal protein synthesis that was corroborated by elevated eIF2B? and rpS6 signaling, without an additional effect of CCL. In summary, a single bout of CCL does not have anabolic effects on skeletal muscle during normal, weight-bearing conditions, even though it has previously been shown to improve regrowth from atrophy. These data demonstrate that interventions that may help recover from atrophy do not necessarily induce muscle hypertrophy in unperturbed conditions.NEW & NOTEWORTHY Massage has been demonstrated to be an effective mechanotherapy to improve recovery from atrophy in adult skeletal muscle; however, this study shows that a single bout of massage fails to increase protein synthesis or anabolic signaling in adult or aged skeletal muscle during normal, weight-bearing conditions. Altogether, our data suggest massage is a useful mechanotherapy for preserving skeletal muscle when combined with other interventions but is not an anabolic stimulus on its own.

Project description:BackgroundExercise intolerance is a cardinal symptom in right (RV) and left ventricular (LV) failure. The underlying skeletal muscle contributes to increased morbidity in patients. Here, we compared skeletal muscle sarcopenia in a novel two-stage model of RV failure to an established model of LV failure.MethodsPulmonary artery banding (PAB) or aortic banding (AOB) was performed in weanling rats, inducing a transition from compensated cardiac hypertrophy (after 7 weeks) to heart failure (after 22-26 weeks). Cardiac function was characterized by echocardiography. Skeletal muscle catabolic/anabolic balance and energy metabolism were analysed by histological and biochemical methods, real-time PCR, and western blot.ResultsTwo clearly distinguishable stages of left or right heart disease with a comparable severity were reached. However, skeletal muscle impairment was significantly more pronounced in LV failure. While the compensatory stage resulted only in minor changes, soleus and gastrocnemius muscle of AOB rats at the decompensated stage demonstrated reduced weight and fibre diameter, higher proteasome activity and expression of the muscle-specific ubiquitin E3 ligases muscle-specific RING finger 1 and atrogin-1, increased expression of the atrophy marker myostatin, increased autophagy activation, and impaired mitochondrial function and respiratory chain gene expression. Soleus and gastrocnemius muscle of PAB rats did not show significant changes in muscle weight and proteasome or autophagy activation, but mitochondrial function was mildly impaired as well. The diaphragm did not demonstrate differences in any model or disease stage except for myostatin expression, which was altered at the decompensated stage in both models. Plasma interleukin (IL)-6 and angiotensin II were strongly increased at the decompensated stage (AOB > > PAB). Soleus and gastrocnemius muscle itself demonstrated an increase in IL-6 expression independent from blood-derived cytokines only in AOB animals. In vitro experiments in rat skeletal muscle cells suggested a direct impact of IL-6 and angiotensin II on distinctive atrophic changes.ConclusionsManifold skeletal muscle alterations are more pronounced in LV failure compared with RV failure despite a similar ventricular impairment. Most of the catabolic changes were observed in soleus or gastrocnemius muscle rather than in the constantly active diaphragm. Mitochondrial dysfunction and up-regulation of myostatin were identified as the earliest signs of skeletal muscle impairment.

Dataset Information

Myoprotective effects of bFGF on skeletal muscle injury in pressure-related deep tissue injury in rats.

Publications

Myoprotective effects of bFGF on skeletal muscle injury in pressure-related deep tissue injury in rats.

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