| Full text | |
| Author(s): |
Martins, Leonardo
;
Amorim, Weslley Wallace
;
Gregnani, Marcos Fernandes
;
Araujo, Ronaldo de Carvalho
;
Qadri, Fatimunnisa
;
Bader, Michael
;
Pesquero, Joao Bosco
Total Authors: 7
|
| Document type: | Journal article |
| Source: | Inflammation Research; v. 72, n. 8, p. 19-pg., 2023-07-18. |
| 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. (AU) | |
| FAPESP's process: | 14/27198-8 - Establishment of a center of genetic and molecular research for clinical challenges |
| Grantee: | João Bosco Pesquero |
| Support Opportunities: | Research Projects - Thematic Grants |
| FAPESP's process: | 15/03541-8 - The role of kinin receptors (B1R and B2R) in the repair of skeletal muscle: new therapeutic approaches to muscle injuries |
| Grantee: | Leonardo Martins Silva |
| Support Opportunities: | Scholarships in Brazil - Doctorate |
| FAPESP's process: | 17/26427-1 - The role of B1 and B2 receptors in fibrosis: a histomorphometric study |
| Grantee: | Leonardo Martins Silva |
| Support Opportunities: | Scholarships abroad - Research Internship - Doctorate |