Tenascin-C-enriched regeneration-specific extracellular matrix guarantees superior muscle regeneration in Ambystoma mexicanum.

Severe muscle injury causes distress and difficulty in humans. Studying the high regenerative ability of the axolotls may provide hints for the development of an effective treatment for severe injuries to muscle tissue. Here, we examined the regenerative process in response to a muscle injury in axolotls. We found that axolotls are capable of complete regeneration in response to a partial muscle resection called volumetric muscle loss (VML), which mammals cannot perfectly regenerate. We investigated the mechanisms underlying this high regenerative capacity in response to VML, focusing on the migration of muscle satellite cells and the extracellular matrix (ECM) formed during VML injury. Axolotls form tenascin-C (TN-C)-enriched ECM after VML injury. This TN-C-enriched ECM promotes the satellite cell migration. We confirmed the importance of TN-C in successful axolotl muscle regeneration by creating TN-C mutant animals. Our results suggest that the maintenance of a TN-C-enriched ECM environment after muscle injury promotes the release of muscle satellite cells and supports eventually high muscle regenerative capacity. In the future, better muscle regeneration may be achieved in mammals through the maintenance of TN-C expression.

Immunohistochemical Comparative Study of Aggressive and Non-aggressive Central Giant Cell Lesions of the Jaws Based on the Tenascin-C Expression Profile.

The purpose of this study was to compare the immunohistochemical expression of tenascin-C (Tn-C) regarding clinicopathological variables and its association with the clinical behavior of central giant cell lesions (CGCLs). Forty-eight paraffin-embedded samples of CGCLs were selected. Based on clinical and radiographic features, the lesions were classified as aggressive (A-CGCLs) and non-aggressive (NA-CGCLs) subtypes. Histological assessment included the microvessel count (MVC), multinucleated giant cell (MGC) count, and the proportion of tissue area involved by mononuclear stromal cells/interstitial fibrosis. Immunoreactivity, immunolocalization, and distribution patterns of Tn-C were studied immunohistochemically. The association between Tn-C expression and clinicopathological characteristics was analyzed separately and adjusted for confounders using logistic regression models. A significantly greater proportion of cases with moderate-to-intense, intracellular, and diffuse staining of Tn-C was observed in A-CGCLs. CGCLs with a size ≥3.3 cm, fast growth, cortical disruption, high MVC/MGC counts, and low interstitial fibrosis showed a significantly greater frequency of moderate-to-intense, intracellular, and diffuse staining. Logistic regression analysis indicated a strong/independent association of these three immunohistochemical parameters with the aggressiveness of lesions. These data appear to suggest a possible role for Tn-C in the etiopathogenesis of CGCLs of the jaws, where its upregulation might favor the destructive behavior of A-CGCLs.

Role of TGF-ß signaling pathway on Tenascin C protein upregulation in a pilocarpine seizure model.

Seizures have been shown to upregulate the expression of numerous extracellular matrix molecules. Tenascin C (TNC) is an extracellular matrix protein involved in several physiological roles and in pathological conditions. Though TNC upregulation has been described after excitotoxins injection, to date there is no research work on the signal transduction pathway(s) participating in TNC protein overproduction. The aim of this study was to evaluate the role of TGF-ß signaling pathway on TNC upregulation. In this study, we used male rats, which were injected with saline or pilocarpine to induce status epilepticus (SE) and killed 24h, 3 and 7 days after pilocarpine administration. For evaluating biochemical changes, we measured protein content of TNC, TGF-ß1 and phospho-Smad2/3 for localization of TNC in coronal brain hippocampus at 24h, 3 and 7 days after pilocarpine-caused SE. We found a significant increase of TNC protein content in hippocampal homogenates after 1, 3, and 7 days of pilocarpine-caused SE, together with an enhancement of TNC immunoreactivity in several hippocampal layers and the dentate gyrus field where more dramatic changes occurred. We also observed a significant enhancement of protein content of both the TGF-ß1 and the critical downstream transduction effector phospho-Smad2/3 throughout the chronic exposure. Interestingly, animals injected with SB-431542, a TGF-ß-type I receptor inhibitor, decreased TNC content in cytosolic fraction and diminished phospho-Smad2/3 content in both cytoplasmic and nuclear fraction compared with pilocarpine vehicle-injected. These findings suggest the participation of TGF-ß signaling pathway on upregulation of TNC which in turn support the idea that misregulation of this signaling pathway produces changes that may contribute to disease.

Estudo imuno-histoquímico da tenascina-C e fibronectina em lesões proliferativas não-neoplásicas de mucosa oral / Immunohistochemistry study of tenascin-C and fibronectin in noneoplasic proliferative lesions of oral mucosa

As lesões proliferativas não-neoplásicas correspondem a respostas teciduais decorrentes de estímulos crônicos de longa duração. Dentro deste grupo enquadra-se o granuloma piogênico, lesão periférica de células gigantes, fibroma ossificante periférico e hiperplasia fibrosa. O objetivo da pesquisa foi observar através da técnica da imuno-histoquímica, se existem diferenças na intensidade, padrão, continuidade e localização da expressão das proteínas da matriz extracelular representadas pela tenascina-C e fibronectina, com a finalidade de contribuir para o melhor entendimento dessas lesões. Utilizou-se 05 casos de cada entidade patológica supracitada, além de 05 espécimes de mucosa oral normal com finalidade comparativa. Observou-se a expressão da tenascina-C e fibronectina na interface epitélio-conjuntivo, bem como na proximidade de vasos sanguíneos nas hiperplasias fibrosas inflamatórias, lesão periférica de células gigantes e fibromas ossificantes, evidenciando o seu envolvimento nos processos de remodelação tecidual. Nossos resultados demonstram que a tenascina-C e a fibronectina são componentes teciduais importantes no desenvolvimento dessas patologias.

The no neoplasic proliferative lesions correspond the tissue reactive originating of long duration chronic stimulus. In this group frame pyogenic granuloma, peripheral giant cell granuloma, peripheral fibroma ossifying and fibrous hyperplasia. The aim of the research was observe, using immunohistochemical technique, if to exist differences in intensity, pattern, continuity and localization of the expression of the proteins of the matrix extrecellar, represent by tenascin-C and fibronectin, with finality of contribute for a best knowledge these lesions. Evaluated 05 cases of each lesion, as well as 05 specimen of normal oral mucosa with comparative finality. It was observed expression in interface conjunctive-epithelium, as well as in the proximity of blood vesseis in the fibrous hyperplasia, peripheral giant cell lesion and ossifying fibroma, evidencing your involvement in the process of improvement of the tissues. Our results demonstrate that those proteins can participate in the development these pathologies, fortifying as soon, your involvement in the process of improvement of the tissues.