DLK1 overexpression improves sepsis-induced cardiac dysfunction and fibrosis in mice through the TGF-β1/Smad3 signaling pathway and MMPs
DLK1 overexpression improves sepsis-induced cardiac dysfunction and fibrosis in mice through the TGF-β1/Smad3 signaling pathway and MMPs
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DOI：
10.1007/s10735-023-10161-6
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发表时间：
2023-09-28
影响因子：
3.2
通讯作者：
Xiao，Feng
中科院分区：
文献类型：
--
作者：
Zeng，Ni;Jian，Zaijin;Xiao，Feng
脓毒症是由细菌感染引起的严重炎症性疾病。心血管功能障碍和重构是脓毒症的严重并发症，可显著影响脓毒症患者的死亡率。delta -样同源物1 （DLK1）可以抑制心肌成纤维细胞分化。然而，DLK1在脓毒症中的作用尚不清楚。在本研究中，首先基于在线数据集GSE79962分析和盲肠结扎和穿刺（CLP）诱导的脓毒症小鼠模型确定DLK1表达。脓毒症心脏组织中DLK1表达显著降低。在脓毒症小鼠心脏，CLP手术降低了缩短分数（EF）（%）和射血分数（FS）（%），引起心肌细胞明显水肿、肌丝排列紊乱、降解和坏死；CLP术后胶原沉积增加，纤维化标志物α-SMA和F-actin蛋白水平升高。DLK1在脓毒症小鼠中过表达可有效提高EF（%）和FS(%)，减弱clp引起的ECM降解和沉积，部分抑制clp诱导的TGF-β1/Smad信号激活。综上所述，clp诱导的脓毒症小鼠心脏中DLK1表达较低。DLK1过表达部分缓解脓毒症诱导的心功能障碍和纤维化，与TGF-β1/Smad3信号通路和MMPs有关。
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.