Chronic inflammation plays a crucial role in vascular calcification. However, only a few studies have revealed the mechanisms underlying the development of inflammation under high-phosphate conditions in chronic kidney disease (CKD) patients. Here, we show that inflammation resulting from the activation of the TGFBR1/TAK1 pathway is involved in calcification in CKD rats or osteogenic medium-cultured human aortic smooth muscle cells (HASMCs). Moreover, miR-135a-5p is demonstrated to be a key regulator of the TGFBR1/TAK1 pathway, which has been reported to be decreased in CKD rats. We further reveal that farnesoid X receptor (FXR) activation increases miR-135a-5p expression, thereby inhibiting the activation of the TGFBR1/TAK1 pathway, ultimately resulting in the attenuation of vascular inflammation and calcification in CKD rats. Our findings provide advanced insights into the mechanisms underlying the development of inflammation in vascular calcification, and evidence that FXR activation could serve as a therapeutic strategy for retarding vascular calcification in CKD patients.

慢性炎症在血管钙化中起着至关重要的作用。然而，只有少数研究揭示了慢性肾病（CKD）患者在高磷酸盐条件下炎症发生的机制。在这里，我们发现 TGFBR1/TAK1 通路激活引起的炎症与 CKD 大鼠或成骨培养基培养的人主动脉平滑肌细胞 (HASMC) 的钙化有关。此外，miR-135a-5p 被证明是 TGFBR1/TAK1 通路的关键调节因子，据报道该通路在 CKD 大鼠中下降。我们进一步发现，法尼醇X受体（FXR）激活会增加miR-135a-5p的表达，从而抑制TGFBR1/TAK1通路的激活，最终导致CKD大鼠血管炎症和钙化的减轻。我们的研究结果提供了对血管钙化炎症发展机制的深入见解，并证明 FXR 激活可以作为延缓 CKD 患者血管钙化的治疗策略。