Kinin receptors regulate skeletal muscle regeneration : differential effects for B1 and B2 receptors

Martins, Leonardo; Amorim, Weslley Wallace; Gregnani, Marcos Fernandes; de Araujo, Ronaldo Carvalho; Qadri, Fatimunnisa; Bader, Michael; Pesquero, Joao Bosco

doi:10.1007/S00011-023-01766-4

Title

Kinin receptors regulate skeletal muscle regeneration : differential effects for B1 and B2 receptors

Author

Martins, Leonardo

Amorim, Weslley Wallace

Gregnani, Marcos Fernandes

de Araujo, Ronaldo Carvalho

Qadri, Fatimunnisa

Bader, Michael

Pesquero, Joao Bosco

Abstract

Objective and designAfter traumatic skeletal muscle injury, muscle healing is often incomplete and produces extensive fibrosis. Bradykinin (BK) reduces fibrosis in renal and cardiac damage models through the B2 receptor. The B1 receptor expression is induced by damage, and blocking of the kallikrein-kinin system seems to affect the progression of muscular dystrophy. We hypothesized that both kinin B1 and B2 receptors could play a differential role after traumatic muscle injury, and the lack of the B1 receptor could produce more cellular and molecular substrates for myogenesis and fewer substrates for fibrosis, leading to better muscle healing.Material and methodsTo test this hypothesis, tibialis anterior muscles of kinin receptor knockout animals were subjected to traumatic injury. Myogenesis, angiogenesis, fibrosis, and muscle functioning were evaluated.ResultsInjured B1KO mice showed a faster healing progression of the injured area with a larger amount of central nucleated fiber post-injury when compared to control mice. In addition, they exhibited higher neovasculogenic capacity, maintaining optimal tissue perfusion for the post-injury phase; had higher amounts of myogenic markers with less inflammatory infiltrate and tissue destruction. This was followed by higher amounts of SMAD7 and lower amounts of p-SMAD2/3, which resulted in less fibrosis. In contrast, B2KO and B1B2KO mice showed more severetissue destruction and excessive fibrosis. B1KO animals had better results in post-injury functional tests compared to control animals.ConclusionsWe demonstrate that injured skeletal muscle tissues have a better repair capacity with less fibrosis in the presence of B2 receptor and absence of B1 receptor, including better performances in functional tests.

Language

English

Source (journal)

Inflammation research. - Basel, 1995, currens

Publication

Basel : Birkhäuser Verlag , 2023

ISSN

1023-3830 [print]

1420-908X [online]

DOI

10.1007/S00011-023-01766-4

Volume/pages