Department of Biomolecular Sciences, Section of Clinical Biochemistry and Molecular Genetics, University "Carlo Bo", 61029 Urbino, Italy.
Department of Angiology, Barbantini Clinic, via del Calcio 2, 55100 Lucca, Italy.
Int J Mol Sci. 2017 Oct 21;18(10):2206. doi: 10.3390/ijms18102206.
Venous leg ulcer (VLU) is a huge healthcare problem with poorly understood pathophysiology. Transforming growth factor-β (TGF-β) and endoglin (Eng), are inflammatory and wound healing mediators. Eng, co-receptor for TGF-β type-II receptors, may be cleaved forming soluble Eng (sEng), antagonizing TGF-β signaling, a crucial process in vascular pathologies. We evaluated the accumulation in wound fluid (WF) of TGF-β isoforms and sEng in healing stages, showing the effects of sulodexide treatments, a glycosaminoglycan with clinical efficacy in VLU healing. Patients with inflammatory (Infl) and granulating (Gran) VLU were recruited. WFs and THP-1 monocytes exposed to Infl and Gran WF (treated/untreated with sulodexide) were analyzed for TGF-β isoforms and sEng by multiplex immunoassay. In both Infl and Gran WF, TGF-β1 and β2 were similar; TGF-β3 was significantly increased in Infl compared to Gran WFs ( = 0.033). sEng was significantly elevated in Gran compared to Infl WFs ( = 0.002). In THP-1 monocytes there was a significant increase in sEng after co-treatment of WF and sulodexide. The increase in TGF-β3 found in Infl WF highlights its negative effect on wound healing, while the increased levels of sEng in Gran WF affects the leukocyte adhesion/transmigration through the endothelium, reducing the inflammatory response and favoring the wound healing. Glycosaminoglycan sulodexide potentiates the effects of sEng release from monocyte, representing an important therapeutic option for wound healing.
静脉性腿部溃疡 (VLU) 是一个严重的医疗保健问题，其病理生理学尚未被充分理解。转化生长因子-β (TGF-β) 和内格林 (Eng) 是炎症和伤口愈合的介质。Eng 是 TGF-β 型 II 受体的共受体，可能被切割形成可溶性 Eng (sEng)，拮抗 TGF-β 信号转导，这是血管病变中的一个关键过程。我们评估了在愈合阶段中，TGF-β 同工型和 sEng 在伤口液 (WF) 中的积累情况，同时展示了 sulodexide 治疗的效果，sulodexide 是一种具有 VLU 愈合临床疗效的糖胺聚糖。招募了患有炎症 (Infl) 和肉芽形成 (Gran) VLU 的患者。通过多重免疫分析法分析 WF 和 THP-1 单核细胞中 TGF-β 同工型和 sEng 的变化，这些单核细胞暴露于 Infl 和 Gran WF（用/未用 sulodexide 处理）。在 Infl 和 Gran WF 中，TGF-β1 和 β2 相似；与 Gran WF 相比，Infl WF 中的 TGF-β3 显著增加（ = 0.033）。与 Infl WF 相比，Gran WF 中的 sEng 显著升高（ = 0.002）。在 WF 和 sulodexide 共同处理后，THP-1 单核细胞中的 sEng 显著增加。在 Infl WF 中发现的 TGF-β3 增加突出了其对伤口愈合的负面影响，而在 Gran WF 中增加的 sEng 水平通过内皮细胞影响白细胞黏附和迁移，从而减少炎症反应并促进伤口愈合。糖胺聚糖 sulodexide 增强了单核细胞中 sEng 释放的作用，代表了伤口愈合的一个重要治疗选择。
