Sepsis is a serious inflammatory disease caused by bacterial infection. Cardiovascular dysfunction and remodeling are serious complications of sepsis, which can significantly affect sepsis patients’ mortality. Delta-like homologue 1 (DLK1) has been reported could inhibit cardiac myofibroblast differentiation. However, the function of DLK1 in sepsis is unknown. In the present study, the DLK1 expression was first identified based on the online dataset GSE79962 analysis and cecal ligation and puncture (CLP)-induced sepsis mouse model. DLK1 expression was significantly reduced in septic heart tissues. In septic mouse heart, CLP operation decreased the fractional shortening (EF) (%) and ejection fraction (FS) (%) and caused significant edema, disordered myofilament arrangement, and degradation and necrosis in myocardial cells; CLP operation also increased collagen deposition and elevated the protein levels of fibrotic markers (α-SMA and F-actin). DLK1 overexpression in septic mice could effectively increase EF (%) and FS (%), attenuate CLP-caused ECM degradation and deposition and partially inhibit the CLP-induced TGF-β1/Smad signaling activation. In conclusion, DLK1 expression was poorly expressed in the CLP-induced septic mouse heart. DLK1 overexpression partially alleviated sepsis-induced cardiac dysfunction and fibrosis, with the involvement of the TGF-β1/Smad3 signaling pathway and MMPs.

脓毒症是一种由细菌感染引起的严重炎症性疾病。心血管功能障碍和重塑是脓毒症的严重并发症，可显着影响脓毒症患者的死亡率。据报道，Delta 样同源物 1 (DLK1) 可以抑制心肌成纤维细胞分化。然而，DLK1 在脓毒症中的功能尚不清楚。在本研究中，DLK1 表达首先根据在线数据集 GSE79962 分析和盲肠结扎穿刺 (CLP) 诱导的脓毒症小鼠模型进行鉴定。脓毒症心脏组织中 DLK1 表达显着降低。在脓毒症小鼠心脏中，CLP手术降低了缩短分数（EF）（%）和射血分数（FS）（%），并引起明显的水肿、肌丝排列紊乱、心肌细胞降解和坏死；CLP 手术还增加了胶原沉积并提高了纤维化标志物（α-SMA 和 F-肌动蛋白）的蛋白质水平。DLK1在脓毒症小鼠中过表达可以有效增加EF（%）和FS（%），减弱CLP引起的ECM降解和沉积，并部分抑制CLP诱导的TGF-β1/Smad信号激活。总之，DLK1 在 CLP 诱导的脓毒症小鼠心脏中表达较差。DLK1 过表达可部分缓解脓毒症引起的心脏功能障碍和纤维化，其中涉及 TGF-β1/Smad3 信号通路和 MMP。