Microphthalmia-associated transcription factor is required for mature myotube formation.

[Background] : The roles of microphthalmia-associated transcription factor (Mitf) in the skeletal muscle and during myogenesis are unclear. [Methods] : Expression of Mitf in mouse tissues and during myogenesis was evaluated. Effects of Mitf knockdown on myogenesis and gene expression related to myogenesis were subsequently explored. Furthermore, effects of p21, a cyclin-dependent kinase inhibitor, and integrin α9 (Itga9) were examined. [Results] : Mitf was highly expressed in the skeletal muscle; Mitf-A and -J were expressed. Mitf expression increased after differentiation stimulation in C2C12 myogenic cells. Down-regulation of Mitf expression by transfection of siRNA for common Mitf inhibited myotube formation, which was reproduced by Mitf-A knockdown. Morphometric analyses indicated that both multinucleated cell number and the proportion of myotubes with more than 6 nuclei were decreased in Mitf-knockdown cells, suggesting that Mitf is required for not only the formation of nascent myotubes but also their maturation. Searching for genes positively regulated by Mitf revealed p21 and Itga9; decreasing Mitf expression inhibited up-regulation of p21 expression after differentiation stimulation and blocked the induction of Itga9 expression in response to differentiation. Knockdown of p21 decreased the number of multinucleated cells, whereas Itga9 knockdown did not affect the myotube number. Both p21 knockdown and Itga9 knockdown decreased the proportion of myotubes with more than 6 nuclei. [General significance] : Mitf positively regulates skeletal muscle formation; Mitf is significantly expressed during myogenesis, and is required for efficient myotube formation through expression of p21 and Itga9

High-Salt Intake Ameliorates Hyperglycemia and Insulin Resistance in WBN/Kob-Leprfa/fa Rats: A New Model of Type 2 Diabetes Mellitus

High-salt intake is a major risk factor for developing hypertension in type 2 diabetes mellitus, but its effects on glucose homeostasis are controversial. We previously found that high-salt intake induces severe hypertension in WBN/Kob diabetic fatty (WBKDF) rats. In the present study, we examined the effects of a high-salt intake on glucose homeostasis in WBKDF rats. Male WBKDF rats and age-matched Wistar rats at 6 weeks of age were each divided into two groups and fed either a normal-sodium (NS, 0.26%) diet or high-sodium (HS, 8%) diet for 7 weeks. Systolic blood pressure and urine volume were increased in WBKDF-HS and Wistar-HS. Body weight gain and food consumption were comparable between NS and HS in both strains. Plasma and urine glucose levels were significantly increased in WBKDF-NS but not in WBKDF-HS. HOMA-IR in WBKDF-HS was significantly lower compared with that in WBKDF-NS. The high plasma adiponectin level in WBKDF-NS compared with that in Wistar-NS was further enhanced in WBKDF-HS. Glycogen deposits and fat droplets in the livers of WBKDF-HS were reduced compared with those of WBKDF-NS. The present study demonstrated that HS intake ameliorated hyperglycemia and insulin resistance in WBKDF rats, which may be due to increased plasma levels of adiponectin

Adaptive expression of uncoupling protein 1 in the carp liver and kidney in response to changes in ambient temperature.

The expression of uncoupling protein (UCP1) is up-regulated in mammalian brown adipocytes during cold exposure. However, a previous study revealed that UCP1 was highly expressed in the liver of common carps, and that the hepatic expression of UCP1 was down-regulated during cold exposure. The present study examined the effects of temperature on the recovery of UCP1 expression levels and the expression of genes involved in UCP1 transcription in the livers and kidneys of common carps. The hepatic and renal expressions of UCP1 were decreased by acclimation from 22 °C to 8 °C, and a subsequent increase in the water temperature from 8 °C to 28 °C recovered the renal, but not hepatic expression of UCP1. Changes in the expression of peroxisome proliferator-activator receptor (PPAR) γ, retinoid X receptor (RXR) α and PPARγ co-activator (PGC)-1α, genes that are involved in the expression of UCP1 in mammals, with ambient temperature indicated that the expressions of PPARγ and RXRα, but not expression of PGC-1α was decreased in response to cold exposure; the hepatic and renal expressions of PPARγ and RXRα recovered to basal levels with the cessation of cold exposure, although this was not complete for hepatic expression of PPARγ. The results of the present study indicate that a unique regulatory mechanism is responsible for the hepatic and renal expressions of carp UCP1 during cold exposure and subsequent reacclimation, and is distinct from that in murine brown adipocytes

Histological Changes in the Placenta Induced by Maternal Alcohol Consumption in the Rat

To investigate the placental enlargement which accompanies maternal alcohol consumption during pregnancy, Sprague-Dawley rats were given 20% ethanol for 4 weeks prior to mating and 30% ethanol throughout gestation. Pair-fed controls received an isocaloric amount of corn starch and chow, with water ad libitum, and ad libitum controls received rat chow and water. On days 17, 18, 19 and 20 of gestation, placentas were removed for histological observation. On days 18–20, the placentas of alcohol-fed rats weighed significantly more than did those of controls, although there was no difference in weight on day 17. Giant cells in the basal zone were significantly increased in number and size in alcohol-fed rats compared to controls. Trophoblastic cells in the basal zone were significantly larger in the alcohol group than in the control groups except on day 17. The maternal blood channels in the labyrinth were wider and more filled with blood corpuscles in the alcohol group than in either control group. It is concluded that the increased weight of the placenta may be largely due to the stagnated maternal blood cells in the labyrinthine blood channels and also to the increased number and size of giant cells and the enlarged trophoblastic cells in the basal zone

母体副腎が胎子膵島細胞の発達に及ぼす影響

妊娠6日目に妊娠ラットの両側副腎除去(ADX)を行い,胎齢14日から16日の胎子膵臓を採取して,母体由来の副腎皮質ホルモンが胎子膵臓内分泌部の発生に及ぼす影響を検討した。母体ADXは胎齢14日以降の膵島および分泌管における細胞分裂を抑制していた。しかしADX群の膵臓では未分化細胞から膵島前駆細胞へのマーカーであるNgn3は増加していた。前者の実験結果から,母体由来の副腎皮質ホルモンは胎子膵島における細胞分裂に関与することが明らかとなった。しかし,それ以降に分化過程(含むシグナル伝達系)にどのように関与しているかについては今後さらに検討すべきであると思われた。To in investigate the effect of maternal adrenocortical hormones on the development of fetal pancreatic islet cells, pregnant rats were adrenalectomized on day 6 of gestation. On days 14-16 the cell division index were estimated. Maternal adrenalectomy resulted in decresed cell division index of both endocrine ducts and pancreatic islets. On day 15, Ngn3, the transcriptional factor that is expressed in epithelial pancreatic progenitor cells before endocrine differentiation, was up regulated in fetal pancreases from ADX group. But maternal adrenalectomy did not alter glucocorticoid receptors mRNA expression. These results suggest that maternal adrenocortical hormones maintain the early development of fetal pancreatic cells, although its action mechanism is not clear