Introduction: Bladder outlet obstruction (BOO) is a common problem that can affect bladder structure and function. Currently, there is no effective treatment options for 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 therapeutic effects on BOO-induced remodeling.
Methods: 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 harvested for histopathology, immunohistochemistry, immunofluorescence, western blot and flow cytometry analysis.
Results: Our results demonstrated that bladder fibrosis was ameliorated by GW250 compared with vehicle group. Furthermore, treatment with GW2580 induced a significant inhibition of macrophage infiltration and M2 macrophage polarization. Pro-fibrotic F4/80+aSMA+ macrophage to myofibroblast transition and CD163+TGF-ß1+ cells were also statistically significant decreased in GW2580 group when compared to vehicle group.
Conclusions: In summary, our findings supported that targeting macrophage through inhibiting CSF-1R signaling might be a promising strategy for the treatment of BOO-induced remodeling.
Source of Funding: This study was supported by the National Natural Science Foundation of China (Grant No. 81800667) and the Innovation Spark Project of Sichuan University (Grant No. 2018SCUH0061).
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