Specific knockdown of m-calpain blocks myogenesis with cDNA deduced from the corresponding RNAi.

Fusion of mononuclear myoblast to multinucleated myotubes is crucial for myogenesis. Both mu- and m-calpain are ubiquitously expressed in most cells and are particularly abundant in muscle cells. Knockout of calpain-1 (catalytic subunit of mu-calpain) induced moderate platelet dysaggregation, preserving the normal development and growth, although knockout of calpain-2 (m-calpain) is lethal in mice.

Which skeletal myoblasts and how to be transplanted for cardiac repair?

Clinical efficacy of skeletal myoblast (skMb) transplantation is controversial whether this treatment produces beneficial outcome in patients with dilated cardiomyopathy (DCM). Based on immunological tolerance between wild-type and DCM hamsters with the deletion of delta-sarcoglycan (SG) gene, skMb engraftment in TO-2 myocardium (3x10(5) cells in approximately 100mg heart) was verified by the donor-specific expression of delta-SG transgene constitutively produced throughout myogenesis. At 5 weeks after the transplantation, the cell rates expressing fast-myosin heavy chain (MHC) exceeded slow-MHC in delta-SG(+) cells.

Gene therapy prevents disruption of dystrophin-related proteins in a model of hereditary dilated cardiomyopathy in hamsters.

Background: The TO-2 hamster is an animal model of dilated cardiomyopathy (DCM). It has genetic and clinical features in common with humans who carry the gene deletion or mutation of the delta-sarcoglycan (SG) gene, a component in dystrophin-related proteins (DRP). DRP stabilise the sarcolemma during cardiac contraction.

Persistent trefoil factor 1 expression imprinted on mouse vaginal epithelium by neonatal estrogenization.

Exposure of female mice to estrogenic substances during the neonatal period induces developmental defects in the reproductive tract such as estrogen-independent persistent proliferation of the vaginal epithelium, which often leads to carcinogenesis in adulthood. In this study, several estrogen-regulated genes have been identified in the neonatal mouse vagina by DNA microarray hybridization analysis. Among the genes up-regulated in the developing vagina by a high dose of estrogen, trefoil factor 1 (TFF1), a mucin-associated gastrointestinal growth factor, showed a unique expression pattern in accordance with the irreversible changes induced by neonatal estrogenization in the vagina.

A novel scheme of dystrophin disruption for the progression of advanced heart failure.

The precise mechanism of the progression of advanced heart failure is unknown. We assessed a new scheme in two heart failure models: (I) congenital dilated cardiomyopathy (DCM) in TO-2 strain hamsters lacking delta-sarcoglycan (SG) gene and (II) administration of a high-dose of isoproterenol, as an acute heart failure in normal rats. In TO-2 hamsters, we followed the time course of the histological, physiological and metabolic the progressions of heart failure to the end stage.

A novel paradigm for therapeutic basis of advanced heart failure--assessment by gene therapy.

The precise mechanism(s) of the progression of advanced heart failure (HF) should be determined to establish strategies for its treatment or prevention. Based on pathological, molecular, and physiological findings in 3 animal models and human cases, we propose a novel scheme that a vicious cycle formed by increased sarcolemma (SL) permeability, preferential activation of calpain over calpastatin, and translocation and cleavage of dystrophin (Dys) commonly lead to advanced HF. The aim of this article was to assess our recent paradigm that disruption of myocardial Dys is a final common pathway to advanced HF, irrespective of its hereditary or acquired origin, but not intended to provide a comprehensive overview of the various factors that may be involved in the course of HF in different clinical settings.

Involvement of keratinocyte growth factor (KGF)-KGF receptor signaling in developmental estrogenization syndrome of mouse vagina.

Exposure of mice to estrogen or keratinocyte growth factor (KGF) in vivo during the neonatal period results in estrogen-independent persistent proliferation and cornification of the vaginal epithelium when the animals become adults. Here, whether and how KGF-signaling is involved in the effects of estrogen on the neonatal mouse vagina were studied with an in vitro method. Newborn mouse vaginae were cultured for 3 days in serum-free medium containing various combinations of estradiol-17beta (E2), KGF, anti-KGF antibody, KGFR inhibitory peptide and heparin, and then transplanted into ovariectomized host mice for 35 days.

Translocation and cleavage of myocardial dystrophin as a common pathway to advanced heart failure: a scheme for the progression of cardiac dysfunction.

Advanced heart failure (HF) is the leading cause of death in developed countries. The mechanism underlying the progression of cardiac dysfunction needs to be clarified to establish approaches to prevention or treatment. Here, using TO-2 hamsters with hereditary dilated cardiomyopathy, we show age-dependent cleavage and translocation of myocardial dystrophin (Dys) from the sarcolemma (SL) to the myoplasm, increased SL permeability in situ, and a close relationship between the loss of Dys and hemodynamic indices.

Neonatal estrogenization leads to increased expression of cellular retinol binding protein 2 in the mouse reproductive tract.

Exposure to estrogenic substances during a time window, the so-called "critical period," in perinatal life causes an irregular development of the genital tract that leads to ovary-independent proliferation and cornification in the vaginal epithelium in mice. We have previously demonstrated that retinol inhibits the irreversible effects of estrogen on the vagina. Here, mice kept in a vitamin-A-deficient condition during perinatal life were shown to be more sensitive to the harmful effects of estrogen.

Vitamin A prevents the irreversible proliferation of vaginal epithelium induced by neonatal injection of keratinocyte growth factor in mice.

Exposure of female mice to estrogen during the perinatal period results in estrogen-independent persistent proliferation and cornification of the vaginal epithelium when the animals become adults. However, the occurrence of such irreversible vaginal changes is blocked by concurrent vitamin A treatment. Neonatal exposure to keratinocyte growth factor (KGF), which is a paracrine mediator of epithelial-mesenchymal interactions, also induces the persistent proliferation and cornification of the vaginal epithelium in adult mice.

Rescue of hereditary form of dilated cardiomyopathy by rAAV-mediated somatic gene therapy: amelioration of morphological findings, sarcolemmal permeability, cardiac performances, and the prognosis of TO-2 hamsters.

The hereditary form comprises approximately 1/5 of patients with dilated cardiomyopathy (DCM) and is a major cause of advanced heart failure. Medical and socioeconomic settings require novel treatments other than cardiac transplantation. TO-2 strain hamsters with congenital DCM show similar clinical and genetic backgrounds to human cases that have defects in the delta-sarcoglycan (delta-SG) gene.