Biomedical subjects

Hiroomi Sensui

Publications and source records attributed to Hiroomi Sensui.

3 recordsLinked to original sources

PubMed2007

Notch2 negatively regulates myofibroblastic differentiation of myoblasts.

Myofibroblasts are one of the key cellular components involved in fibrosis of skeletal muscle as well as in other tissues. Transforming growth factor-beta1 (TGF-beta1) stimulates differentiation of mesenchymal cells into myofibroblasts, but little is known about the regulatory mechanisms of myofibroblastic differentiation. Since Notch2 was shown to be downregulated in TGF-beta1-induced non-muscle fibrogenic tissue, we investigated whether Notch2 also has a distinctive role in myofibroblastic differentiation of myogenic cells induced by TGF-beta1. TGF-beta1 treatment of C2C12 myoblasts led to expression of myofibroblastic marker alpha-smooth muscle actin (alpha-SMA) and collagen I with concomitant downregulation of Notch2 expression. Overexpression of active Notch2 inhibited TGF-beta1-induced expression of alpha-SMA and collagen I. Interestingly, transient knockdown of Notch2 by siRNA in C2C12 myoblasts and primary cultured muscle-derived progenitor cells resulted in differentiation into myofibroblastic cells expressing alpha-SMA and collagen I without TGF-beta1 treatment. Furthermore, we found Notch3 was counter-regulated by Notch2 in C2C12 cells. These findings suggest that Notch2 is inhibiting differentiation of myoblasts into myofibroblasts with downregulation of Notch3 expression.

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PubMed2006

Knockdown of hypoxia-inducible factor-1alpha by siRNA inhibits C2C12 myoblast differentiation.

We analyzed the role of Hypoxia-inducible factor (HIF)-1alpha in myoblast differentiation by examining the expression and regulation of HIF-1alpha in proliferating and differentiating C2C12 myoblast, and by knocking down HIF-1alpha of C2C12 myoblasts with small interfering RNA (siRNA), given that HIF-1alpha has been shown to be involved in differentiative process in non-muscle tissues. Although HIF-1alpha mRNA was constantly expressed in C2C12 myoblasts both under growth and differentiating phase, HIF-1alpha protein was hardly detectable in the growth phase but became detectable only during myogenic differentiation even under normoxia. During early stage of C2C12 myogenesis, HIF-1alpha accumulated in the nuclei of myogenin-positive myoblasts. The inhibition of proteasome in the growth phase led to HIF-1alpha protein accumulation, whereas in the differentiation phase the inhibition of Hsp90, which stabilizes HIF-1alpha, suppressed HIF-1alpha accumulation. Therefore, we suggest that the level of HIF-1alpha protein expression is regulated by a proteasome-and chaperon-dependent pathway in C2C12 myoblast. Knockdown of HIF-1alpha effectively blocked myotube formation and myosin heavy chain (MHC) expression. Finally, HIF-1alpha expression in vivo was confirmed in the regenerative muscle tissue of mice after eccentric exercise. We conclude that HIF-1alpha is required for C2C12 myogenesis in vitro, and suggest that HIF-1alpha may have an essential role in regenerative muscle tissue in vivo.

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PubMed2004

Myofibers express IL-6 after eccentric exercise.

BACKGROUND: Interleukin (IL)-6 is locally produced in skeletal muscles and shows a remarkable increase in plasma after eccentric exercises. OBJECTIVE: To elucidate the cell types in the muscles responsible for IL-6 production after eccentric exercises. STUDY DESIGN: Controlled laboratory study. METHODS: An eccentric contraction model was made using electrical stimulation. The authors investigated the muscle damage and regeneration processes after eccentric exercises histologically, and the cell types expressing IL-6 and its subcellular compartimentalization with time immunohistochemically after eccentric exercises. RESULTS: Swollen myofibers were detected from 8 hours to 3 days after exercises. Disrupted myofibers were detected from 24 hours to 7 days, with a peak of 3 days. IL-6 was detected only in the cytoplasm of myofibers until 12 hours; thereafter, it was found in the inflammatory cells and proliferating satellite cells as well. The swollen myofibers were negatively stained for IL-6. The positive ratios of IL-6 in myofibers immediately increased after exercises, peaked in 12 hours, and then decreased. CONCLUSIONS: After eccentric exercises, IL-6 expression increased in myofibers preceding the disruption of myofibers. IL-6 might be closely related to muscle damage caused by strenuous exercises.

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