■尿道狭窄对患者和临床医生都是临床挑战。创伤后尿道狭窄与由过度炎症引起的瘢痕组织的形成有关。这项研究的目的是探索这种疾病的潜在治疗策略。
■进行了新西兰兔体内实验和THP-1单核细胞和尿道成纤维细胞的体外实验,以研究从IL-1β处理的间充质干细胞(Exo-MSCsIL-1β)分离的外泌体对创伤后尿道狭窄的影响以及巨噬细胞M2极化在此过程中的作用。此外,探讨了相关的信号传导和背后的机制。
■在新西兰兔创伤后尿道狭窄模型中,与Exo-MSCs相比,注射Exo-MSCsIL-1β可显着减少尿道狭窄和胶原纤维积累。向THP-1单核细胞中添加Exo-MSCsIL-1β在体外诱导的M2巨噬细胞极化中,which,反过来,抑制尿道成纤维细胞的活化和胶原的合成。机械上,Exo-MSCsIL-1β被发现含有高水平的microRNAlet-7c,荧光素酶报告分析表明let-7c与PAK1mRNA的3UTR相互作用。用let-7c模拟物转染THP-1细胞下调PAK1表达并抑制NF-κB信号通路的激活。
■这些结果支持含有let-7c的Exo-MSCsIL-1β通过抑制PAK1-NF-κB信号传导在减少尿道狭窄中的作用,M2巨噬细胞极化,和尿道肌成纤维细胞的分化。
UNASSIGNED: Urethral stricture is a clinical challenge for both patients and clinicians. Post-traumatic urethral stricture is associated with formation of scar tissue caused by excessive inflammation. The aim of this study is exploring potential therapeutic strategies for this condition.
UNASSIGNED: In vivo experiments on New Zealand rabbits and in vitro experiments on THP-1 monocytes and urethral fibroblasts were performed to investigate the effects on post-traumatic urethral stricture of exosomes isolated from IL-1β-treated mesenchymal stem cells (Exo-MSCsIL-1β) and the role of macrophage M2 polarization in this process. Additionally, related signaling and mechanism behind were explored.
UNASSIGNED: In a New Zealand rabbit model of post-traumatic urethral stricture, injection of Exo-MSCsIL-1β significantly reduced urethral stricture and collagen fiber accumulation compared with Exo-MSCs. Addition of Exo-MSCsIL-1β to THP-1 monocytes in vitro induced M2 macrophage polarization, which, in turn, inhibited activation of urethral fibroblasts and synthesis of collagen. Mechanistically, Exo-MSCsIL-1β were found to contain high levels of the microRNA let-7c, and luciferase reporter assays showed that let-7c interacted with the 3\'UTR of PAK1 mRNA. Transfection of THP-1 cells with a let-7c mimic downregulated PAK1 expression and inhibited activation of the NF-κB signaling pathway.
UNASSIGNED: These results support a role for let-7c-containing Exo-MSCsIL-1β in reducing urethral stricture via inhibition of PAK1-NF-κB signaling, M2 macrophage polarization, and differentiation of urethral myofibroblasts.