Leucine supplementation accelerates connective tissue repair of injured tibialis anterior muscle.

This study investigated the effect of leucine supplementation on the skeletal muscle regenerative process, focusing on the remodeling of connective tissue of the fast twitch muscle tibialis anterior (TA). Young male Wistar rats were supplemented with leucine (1.35 g/kg per day); then, TA muscles from the left hind limb were cryolesioned and examined after 10 days. Although leucine supplementation induced increased protein synthesis, it was not sufficient to promote an increase in the cross-sectional area (CSA) of regenerating myofibers (p > 0.05) from TA muscles. However, leucine supplementation reduced the amount of collagen and the activation of phosphorylated transforming growth factor-ß receptor type I (TßR-I) and Smad2/3 in regenerating muscles (p < 0.05). Leucine also reduced neonatal myosin heavy chain (MyHC-n) (p < 0.05), increased adult MyHC-II expression (p < 0.05) and prevented the decrease in maximum tetanic strength in regenerating TA muscles (p < 0.05). Our results suggest that leucine supplementation accelerates connective tissue repair and consequent function of regenerating TA through the attenuation of TßR-I and Smad2/3 activation. Therefore, future studies are warranted to investigate leucine supplementation as a nutritional strategy to prevent or attenuate muscle fibrosis in patients with several muscle diseases.

Arrangement and fine structure of collagen fibrils in the decidualized mouse endometrium.

The adaptations of the mouse uterus to pregnancy include extensive modifications of the cells and extracellular matrix of the endometrial connective tissue that surround the embryos. Around each implanted embryo this tissue redifferentiates into a transient structure called decidua, which is formed by polygonal cells joined by intercellular junctions. In the mouse, thick collagen fibrils with irregular profile appear in decidualized areas of the endometrium but not in the nondecidualized stroma and interimplantation sites. The fine organization of these thick fibrils has not yet been established. This work was addressed to understand the arrangement and fine structure of collagen fibrils of the decidua of pregnant mice during the periimplantation stage. Major modifications occurred in collagen fibrils that surrounded decidual cells: (1) the fibrils, which were arranged in parallel bundles in nonpregnant animals, became organized as baskets around decidual cells; (2) very thick collagen fibrils with very irregular profiles appeared around decidual cells. Analysis of replicas and serial sections suggests that the thick collagen fibrils form by the lateral aggregation of thinner fibrils to a central fibril resulting in very irregular profile observed in cross sections of thick fibrils. The sum of modifications of the collagen fibrils seem to represent an adaptation of the endometrium to better support the decidual cells while they hold the embryos during the beginning of their development. The deposition of thick collagen fibrils in the decidua may contribute to form a barrier that impedes leukocyte migration within the decidua, preventing immunological rejection of genetically dissimilar embryonic tissues.

Modulation of hyaluronan in the migratory pathway of mouse primordial germ cells.

In the present report we followed the distribution of hyaluronan during the phases of separation, migration, and colonization of the primordial germ cell migratory process. Hyaluronan was detected by the use of two cytochemical methods: (1) ruthenium hexammine trichloride (RHT) associated with enzymatic treatment with hyaluronate lyase and (2) a binding specific probe for hyaluronan. After RHT treatment the proteoglycans and/or glycosaminoglycans were observed as a meshwork formed by electron-dense granules connected by thin filaments. After enzymatic digestion, no filaments could be detected in the migratory pathway. Quantitative analysis showed a close correlation between cell migration and the concentration of RHT-positive filaments. It was also shown that high amounts of hyaluronan were expressed in the separation phase and migration phases whereas during the colonization phase the amount of hyaluronan was clearly diminished. This study showed that the presence of primordial germ cells in each compartment of the migratory pathway was always accompanied by a high expression of hyaluronan. These results indicate that hyaluronan is an important molecule in the migratory process, providing the primordial germ cells with a hydrated environment that facilitates their movement toward the genital ridges.