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Hypertrophic Response (hypertrophic + response)
Selected AbstractsOverload-induced skeletal muscle extracellular matrix remodelling and myofibre growth in mice lacking IL-6ACTA PHYSIOLOGICA, Issue 4 2009J. P. White Abstract Aim:, Overloading healthy skeletal muscle produces myofibre hypertrophy and extracellular matrix remodelling, and these processes are thought to be interdependent for producing muscle growth. Inflammatory cytokine interleukin-6 (IL-6) gene expression is induced in overloaded skeletal muscle, and the loss of this IL-6 induction can attenuate the hypertrophic response to overload (OV). Although the OV induction of IL-6 in skeletal muscle may be an important regulator of inflammatory processes and satellite cell proliferation, less is known about its role in the regulation of extracellular matrix remodelling. The purpose of the current study was to examine if OV-induced extracellular matrix remodelling, muscle growth, and associated gene expression were altered in mice that lack IL-6, when compared with wild-type mice. Methods:, Male C57/BL6 (WT) and C57/BL6 × IL-6,/, (IL-6,/,) mice (10 weeks of age) were assigned to either a sham control or synergist ablation OV treatments for 3, 21 or 56 days. Result:, Plantaris muscle mass increased 59% in WT and 116% in IL-6,/, mice after 21 day OV. Myofibre CSA was also increased by 21 day OV in both WT and IL-6,/, mice. OV induced a twofold greater increase in the volume of non-contractile tissue in IL-6,/, muscle compared to WT. OV also induced a significantly greater accumulation of hydroxyproline and procollagen-1 mRNA in IL-6,/, muscle, when compared with WT muscle after 21 day OV. Transforming growth factor-, and insulin-like growth factor-1 mRNA expression were also induced to a greater extent in IL-6,/, muscle when compared with WT muscle after 21 day OV. There was no effect of IL-6 loss on the induction of myogenin, and cyclin D1 mRNA expression after 3 day OV. However, MyoD mRNA expression in 3 day OV IL-6,/, muscle was attenuated when compared with WT OV mice. Conclusion:, IL-6 appears to be necessary for the normal regulation of extracellular matrix remodelling during OV-induced growth. [source] Angiotensin-Converting Enzyme Genotype Affects the Response of Human Skeletal Muscle to Functional OverloadEXPERIMENTAL PHYSIOLOGY, Issue 5 2000Jonathan Folland The response to strength training varies widely between individuals and is considerably influenced by genetic variables, which until now, have remained unidentified. The deletion (D), rather than the insertion (I), variant of the human angiotensin-converting enzyme (ACE) genotype is an important factor in the hypertrophic response of cardiac muscle to exercise and could also be involved in skeletal muscle hypertrophy , an important factor in the response to functional overload. Subjects were 33 healthy male volunteers with no experience of strength training. We examined the effect of ACE genotype upon changes in strength of quadriceps muscles in response to 9 weeks of specific strength training (isometric or dynamic). There was a significant interaction between ACE genotype and isometric training with greater strength gains shown by subjects with the D allele (mean ± S.E.M.: II, 9.0 ± 1.7%; ID, 17.6 ± 2.2%; DD, 14.9 ± 1.3%, ANOVA, P 0.05). A consistent genotype and training interaction (ID DD II) was observed across all of the strength measures, and both types of training. ACE genotype is the first genetic factor to be identified in the response of skeletal muscle to strength training. The association of the ACE I/D polymorphism with the responses of cardiac and skeletal muscle to functional overload indicates that they may share a common mechanism. These findings suggest a novel mechanism, involving the renin-angiotensin system, in the response of skeletal muscle to functional overload and may have implications for the management of conditions such as muscle wasting disorders, prolonged bed rest, ageing and rehabilitation, where muscle weakness may limit function. [source] Serum HGF and TGF-,1 levels after right portal vein embolizationHEPATOLOGY RESEARCH, Issue 3 2010Hiromitsu Hayashi Aim:, The changes in the serum hepatocyte growth factor (HGF) and transforming growth factor (TGF)-beta1 levels after portal vein embolization (PVE), and their clinical significance, remain unclear and we aimed to assess their relationship. Methods:, The serum HGF and TGF-beta1 levels were prospectively measured in 22 patients before and 1, 3, 5, 7, and 14 day after right PVE. Computed tomographic volumetry was performed before and at a mean of 26 ± 4 days after right PVE. Results:, Three to four weeks after right PVE, the volume of embolized lobe significantly decreased from 704 ± 157 cm3 before PVE to 539 ± 168 cm3 after PVE (P < 0.001). In contrast, the volume of nonembolized lobe significantly increased from 426 ± 142 cm3 to 560 ± 165 cm3 (P < 0.001). The serum HGF level significantly increased on day 3 after PVE compared with the pretreatment level (P = 0.005), while the serum TGF-beta1 level significantly decreased and reached its lowest value on day 3 (P = 0.002). Using Pearson's correlation analysis, we found that the serum HGF and TGF-beta1 levels on day 14 negatively associated with the large hypertrophic response in the nonembolized lobe (HGF: r = ,0.490, P = 0.021; TGF-beta1: r = ,0.473, P = 0.026). Conclusions:, PVE induced an increase in the serum HGF level and reduced the serum TGF-beta1 level. Measurement of serum HGF and TGF-beta1 levels on day 14 after right PVE may be useful for assessment of the future liver hypertrophy in nonembolized lobe after right PVE. [source] Cellular repressor of E1A-stimulated genes attenuates cardiac hypertrophy and fibrosisJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 7 2009Zhouyan Bian Abstract Cellular repressor of E1A-stimulated genes (CREG) is a secreted glycoprotein of 220 amino acids. It has been proposed that CREG acts as a ligand that enhances differentiation and/or reduces cell proliferation. CREG has been shown previously to attenuate cardiac hypertrophy in vitro. However, such a role has not been determined in vivo. In the present study, we tested the hypothesis that overexpression of CREG in the murine heart would protect against cardiac hypertrophy and fibrosis in vivo. The effects of constitutive human CREG expression on cardiac hypertrophy were investigated using both in vitro and in vivo models. Cardiac hypertrophy was produced by aortic banding and infusion of angiotensin II in CREG transgenic mice and control animals. The extent of cardiac hypertrophy was quantitated by two-dimensional and M-mode echocardiography as well as by molecular and pathological analyses of heart samples. Constitutive over-expression of human CREG in the murine heart attenuated the hypertrophic response, markedly reduced inflammation. Cardiac function was also preserved in hearts with increased CREG levels in response to hypertrophic stimuli. These beneficial effects were associated with attenuation of the mitogen-activated protein kinase (MAPK)-extracellular signal-regulated kinase 1 (MEK-ERK1)/2-dependent signalling cascade. In addition, CREG expression blocked fibrosis and collagen synthesis through blocking MEK-ERK1/2-dependent Smad 2/3 activation in vitro and in vivo. Therefore, the expression of CREG improves cardiac functions and inhibits cardiac hypertrophy, inflammation and fibrosis through blocking MEK-ERK1/2-dependent signalling. [source] The role of phosphoinositide 3-kinase and phosphatidic acid in the regulation of mammalian target of rapamycin following eccentric contractionsTHE JOURNAL OF PHYSIOLOGY, Issue 14 2009T. K. O'Neil Resistance exercise induces a hypertrophic response in skeletal muscle and recent studies have begun to shed light on the molecular mechanisms involved in this process. For example, several studies indicate that signalling by the mammalian target of rapamycin (mTOR) is necessary for a hypertrophic response. Furthermore, resistance exercise has been proposed to activate mTOR signalling through an upstream pathway involving the phosphoinositide 3-kinase (PI3K) and protein kinase B (PKB); however, this hypothesis has not been thoroughly tested. To test this hypothesis, we first evaluated the temporal pattern of signalling through PI3K,PKB and mTOR following a bout of resistance exercise with eccentric contractions (EC). Our results indicated that the activation of signalling through PI3K,PKB is a transient event (<15 min), while the activation of mTOR is sustained for a long duration (>12 h). Furthermore, inhibition of PI3K,PKB activity did not prevent the activation of mTOR signalling by ECs, indicating that PI3K,PKB is not part of the upstream regulatory pathway. These observations led us to investigate an alternative pathway for the activation of mTOR signalling involving the synthesis of phosphatidic acid (PA) by phospholipase D (PLD). Our results demonstrate that ECs induce a sustained elevation in [PA] and inhibiting the synthesis of PA by PLD prevented the activation of mTOR. Furthermore, we determined that similar to ECs, PA activates mTOR signalling through a PI3K,PKB-independent mechanism. Combined, the results of this study indicate that the activation of mTOR following eccentric contractions occurs through a PI3K,PKB-independent mechanism that requires PLD and PA. [source] Silibinin attenuates cardiac hypertrophy and fibrosis through blocking EGFR-dependent signaling,JOURNAL OF CELLULAR BIOCHEMISTRY, Issue 5 2010Wen Ai Abstract Cardiac hypertrophy is a major determinant of heart failure. The epidermal growth factor receptor (EGFR) plays an important role in cardiac hypertrophy. Since silibinin suppresses EGFR in vitro and in vivo, we hypothesized that silibinin would attenuate cardiac hypertrophy through disrupting EGFR signaling. In this study, we examined this hypothesis using neonatal cardiac myocytes and fibroblasts induced by angiotensin II (Ang II) and animal model by aortic banding (AB) mice. Our data revealed that silibinin obviously blocked cardiac hypertrophic responses induced by pressure overload. Meanwhile, silibinin markedly reduced the increased generation of EGFR. Moreover, these beneficial effects were associated with attenuation of the EGFR-dependent ERK1/2, PI3K/Akt signaling cascade. We further demonstrated silibinin decreased inflammation and fibrosis by blocking the activation of NF-,B and TGF-,1/Smad signaling pathways in vitro and in vivo. Our results indicate that silibinin has the potential to protect against cardiac hypertrophy, inflammation, and fibrosis through blocking EGFR activity and EGFR-dependent different intracellular signaling pathways. J. Cell. Biochem. 110: 1111,1122, 2010. Published 2010 Wiley-Liss, Inc. [source] | |||||||||||||