The preventive effects of colony-stimulating factor 1 receptor (CSF-1R) inhibition on bladder outlet obstruction induced remodeling.
Neurourol Urodyn
; 41(3): 787-796, 2022 03.
Article
em En
| MEDLINE
| ID: mdl-35170790
ABSTRACT
INTRODUCTION:
Bladder outlet obstruction (BOO) is a common problem that can affect bladder structure and function. Currently, there is no effective drugs available to prevent BOO-induced remodeling. Previous reports have demonstrated that the pathogenesis of BOO is associated with macrophage infiltration and polarization, which is physiologically dependent on colony-stimulating factor 1 receptor (CSF-1R) activation. Here we utilized a highly selective CSF-1R inhibitor, GW2580, to determine its preventive effects on BOO-induced remodeling.METHODS:
A total of 24 Sprague-Dawley rats were randomly divided into sham, BOO + vehicle, and BOO + GW2580 group. GW2580 or vehicle control was administrated by oral gavage at daily doses of 40 mg/kg for 6 weeks. Bladder samples were collected for histopathology, immunohistochemistry, immunofluorescence, western blotting, and flow cytometry analysis.RESULTS:
Our results demonstrated that bladder fibrosis was ameliorated by GW2580 compared with the vehicle group (22.01% ± 5.13% vs. 32.15% ± 7.24%, p < 0.01). Furthermore, treatment with GW2580 induced an inhibition of macrophage infiltration (4.41% ± 1.28% vs. 13.57% ± 3.42%, p < 0.001) and M2 macrophage polarization (10.67% ± 4.15% vs. 28.59% ± 6.38%, p < 0.001). There was also a decrease of profibrotic F4/80+ α-smooth muscle actin+ (α-SMA+ ) macrophage to myofibroblast transition (9.11% ± 2.58% vs. 17.33% ± 4.01%, p < 0.001) and CD163+ TGF-ß1+ cells (7.68% ± 2.10% vs. 14.17% ± 4.09%, p < 0.01) in the GW2580 group when compared with the vehicle group.CONCLUSIONS:
In summary, our findings showed that GW2580 is a worthwhile candidate for a follow-up study to test in the treatment of BOO-induced remodeling.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Obstrução do Colo da Bexiga Urinária
Tipo de estudo:
Observational_studies
/
Prognostic_studies
Limite:
Animals
/
Female
/
Humans
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Male
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article