KLF13 overexpression protects sepsis‐induced myocardial injury and LPS‐induced inflammation and apoptosis

Abstract

Sepsis remains a worldwide public health problem. This study aims to explore the role and mechanism of transcriptional factors (TFs) in sepsis-induced myocardial injury. Firstly, TF KLF13 was selected to explore its role in sepsis-induced myocardial injury. The caecal ligation and puncture (CLP) -induced sepsis mouse model was established and the septic mice were examined using standard histopathological methods. KLF13 expression was detected in the septic mouse heart and was also seen in a lipoploysaccharide (LPS) -induced cellular inflammation model. To explore this further both pro-apoptotic cleaved-caspase3/caspase3 and Bax levels and anti-apoptotic Bcl2 levels were examined, also in both models, In addition inflammatory cytokine (IL-1β, TNF-α, IL-8 and MCP-1) production and IκB-α protein level and p65 phosphorylation were examined in both septic mice and LPS-induced cells. Thus three parameters -cardiomyocyte apoptosis, inflammatory response and NF-κB pathway activation were evaluated under similar conditions. The septic mice showed significant oedema, disordered myofilament arrangement and degradation and necrosis to varying degrees in the myocardial cells. KLF13 was downregulated in both the septic mouse heart and the LPSinduced cellular inflammation model. Furthermore, both models showed abnormally increased cardiomyocyte apoptosis (increased cleaved-caspase3/caspase and Bax protein levels and decreased Bcl2 level), elevated inflammation (increased production of inflammatory cytokines) and the activated NF-κB pathway (increased p65 phosphorylation and decreased IκB-α protein level). KLF13 overexpression notably ameliorated sepsis-induced myocardial injury in vivo and in vitro. KLF13 overexpression protected against sepsis-induced myocardial injury and LPS-induced cellular inflammation and apoptosis via inhibiting the inflammatory pathways (especially NF-κB signalling) and cardiomyocyte apoptosis.

Pretreatment with interleukin-15 attenuates inflammation and apoptosis by inhibiting NF-κB signaling in sepsis-induced myocardial dysfunction

“…Our findings are consistent with previous results that excessive cardiomyocyte apoptosis is tightly related to cardiac dysfunction in the CLP-induced sepsis model. 35 , 36 In addition, one study showed that IL-15 protected hypoxia-induced cardiomyocyte death through activation of STAT3 and PI3K-ERK1/2 pathways, 13 which maybe other possible mechanisms that contribute to the cardioprotective effect of IL-15. Finally, Inoue et al .…”

Cecropin A Alleviates LPS-Induced Oxidative Stress and Apoptosis of Bovine Endometrial Epithelial Cells

“…Antioxidant enzymes, including SOD, SOD2, and peroxidases such as GPX and CAT, play a crucial role in antioxidant defense by regulating ROS levels [ 33 , 34 ]. A high concentration of LPS leads to abnormal ROS and MMP levels; promotes the production of inflammatory factors such as TNF-α, IL-1β, IL-6, and IL-8, causing oxidative damage and mitochondrial dysfunction [ 2 , 35 ]; and even leads to apoptosis [ 36 , 37 ]. Cecropin A has been shown to inhibit the production of TNF-α and IL-1β induced by LPS in mouse macrophage-derived RAW264.7 cells [ 18 ].…”

Xijiao Dihuang Decoction Protects Against Murine Sepsis-Induced Cardiac Inflammation and Apoptosis via Suppressing TLR4/NF-κB and Activating PI3K/AKT Pathway

“…As an antipyretic agent, XJDHT exhibits potent anti-inflammation effects and can decrease the expression of adhesion molecules by vascular endothelial cells. 23 , 33 , 34 Previous study demonstrated that XJDHT reduces the release of inflammatory cytokines such as IL-6 and improves survival in rats with sepsis via regulation of the HIF-1α signaling pathway. 18 Recent studies have reported that XJDHT suppresses aerobic glycolysis by down-regulating the TLR4/HIF-1α/PKM2 signaling pathway, therebyimproving prognosis in sepsis.…”

“…Growing evidence suggests that most patients with septic shock suffer from myocardial depression. 19 The mechanisms underlying myocardial depression during sepsis predominantly include mitochondrial dysfunction, 20,21 cell death (necrosis and apoptosis), 22,23 and inflammation. 24,25 LPS is highly pathogenic and can induce severe sepsis, [26][27][28][29] accordingly, LPS is often used to induce myocardial injury in animal models.…”