Navegando por Palavras-chave "Kinin Receptors"

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    O papel dos receptores B1 e B2 de cininas no reparo do músculo esquelético
    (Universidade Federal de São Paulo (UNIFESP), 2020-12-18) Silva, Leonardo Martins [UNIFESP]; Pesquero, Joao Bosco [UNIFESP]; Universidade Federal de São Paulo
    Fibrosis is characterized by an excessive accumulation of extracellular matrix components, being one of the main sequelae acquired after muscle injury. In severe injuries, where healing occurs slowly, fibrosis prevents proper muscle contraction and can lead to muscle contractures and chronic pain. Besides being an important aggravating factor of muscular dystrophies, it is also one of the main causes that lead professional and amateur athletes to abandon their activities early. The study of factors leading to fibrosis reduction and muscle regeneration is strongly relevant. Modulation of B1R and B2R receptor activity of the kallikrein-kinin system has shown benefits in the application of some pathophysiology and, more recently, in tissue regeneration, however, there is a need to better understand this mechanism in skeletal muscle. In this study we assess that animals knocked out for B1 and B2 kinin receptors have histomorphological, cellular and molecular differences regarding post-injury tissue repair when compared to wild-type (WT) animals in the days following the injury. Kinin B2-Receptor Knockout Mice (B2KO) show a pattern of structural disorganization and intense tissue fibrosis in macroscopic evaluations from the 15th post-injury day, when compared with WT animals. Kinin B1-Receptor Knockout Mice (B1KO) showed better performance in post-injury functional tests from the 4th day on, presenting an excellent ability to recover post-injury performance. These animals also showed greater angiogenic capacity, greater regenerative potential and decreased fibrosis through suppression of Col1a via the TGF-β/Smads pathway. Our data also showed that B2KO and B1B2KO animals showed intense tissue destruction, with low myogenic capacity, excessive fibrosis and loss of performance in post-injury functional tests. The results presented in the study corroborate the hypothesis that a probable blockade of the B1 receptor, and/or the overexpression/activation of the B2 receptor in the early stages of acute injury, provide better conditions for maintaining the repair with less fibrosis and gain in function. Therefore, they contribute to the development of new therapeutic tools for musculoskeletal injuries associated with the kallikrein-kinin system and its receptors.