MircoRNA-145 promotes activation of hepatic stellate cells via targeting krüppel-like factor 4

Men, Ruoting; Wen, Maoyao; Zhao, Mingyue; Dan, Xuelian; Wu, Wenchao; Wang, Maggie Haitian; Liu, Xiaojing; Yang, Li

doi:10.1038/srep40468

Cited by 24 publications

(22 citation statements)

References 35 publications

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“…Consistent with this, in the liver fibrosis model, KLF4 expression was decreased in hepatic stellate cells [71]. In addition, according to Men and his colleague's research, KLF4 was reduced in activated hepatic stellate cells (HSCs) and cirrhotic liver tissues and KLF4 deficiency promote HSC activation [72]. Another study suggests that other mechanisms independent of IL-4 may also regulate the M2 phenotype [73].…”

Section: Discussionmentioning

confidence: 80%

C/EBP Homologous Protein (CHOP) Activates Macrophages and Promotes Liver Fibrosis inSchistosoma japonicum-Infected Mice

Duan

Yang

Peng

et al. 2019

Journal of Immunology Research

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CCAAT/enhancer-binding homologous protein (CHOP), a transcriptional regulator induced by endoplasmic reticulum stress (ER stress) is a pivotal factor in the ER stress-mediated apoptosis pathway. Previous studies have shown that CHOP is involved in the formation of fibrosis in a variety of tissues and is associated with alternative macrophage activation. The role of CHOP in the pathologic effects of liver fibrosis in schistosomiasis has not been reported, and underlying mechanisms remain unclear. This study is aimed at understanding the effect of CHOP on liver fibrosis induced by Schistosoma japonicum (S. japonicum) in vivo and clarifying its mechanism. C57BL/6 mice were infected with cercariae of S. japonicum through the abdominal skin. The liver fibrosis was examined. The level of IL-13 was observed. The expressions of CHOP, Krüppel-like factor 4 (KLF4), signal transducer and activator of transcription 6 (STAT6), phosphorylation STAT6, interleukin-13 receptor alpha 1 (IL-13Rα1), and interleukin-4 receptor alpha (IL-4Rα) were analysed. The eosinophilic granuloma and collagen deposition were found around the eggs in mice infected for 6 and 10 weeks. IL-13 in plasma and IL-13Rα1 and IL-4Rα in liver tissue were significantly increased. The phosphorylated STAT6 was enhanced while Krüppel-like factor 4 (KLF4) was decreased in liver tissue. The expression of CHOP and colocalization of CHOP and CD206 were increased. Overall, these results suggest that CHOP plays a critical role in hepatic fibrosis induced by S. japonicum, likely through promoting alternative activation of macrophages.

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Section: Discussionmentioning

confidence: 80%

C/EBP Homologous Protein (CHOP) Activates Macrophages and Promotes Liver Fibrosis inSchistosoma japonicum-Infected Mice

Duan

Yang

Peng

et al. 2019

Journal of Immunology Research

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“…In addition, microRNA-145 antagonism reverses the TGF-␤ inhibition of F508del cystic fibrosis transmembrane conductance regulator correction in airway epithelia (19). Furthermore, it was reported that miR-145 was up-regulated in activated rat primary hepatic stellate cells (HSCs) and TGF-␤-treated HSCs, which contributed to liver fibrosis (20). However, whether miR-145 regulates peritoneal fibrosis in the development of PD remains unknown.…”

Section: Peritoneal Fibrosis Is a Common Complication Of Long-term Pementioning

confidence: 99%

MicroRNA-145 promotes the epithelial-mesenchymal transition in peritoneal dialysis-associated fibrosis by suppressing fibroblast growth factor 10

Huang

et al. 2019

Journal of Biological Chemistry

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“…KLF4, a gut-enriched GKLF and zinc-finger transcription factor, regulates a multitude of processes in cell growth and development, proliferation and differentiation, inflammation, and apoptosis, and is even both a tumor suppressor and oncogene. A recent study reported that the expression of KLF4 declines dramatically in activated rat HSCs in the liver tissues of cirrhotic patients [34]. To determine whether KLF4 protects against CCl 4 -induced acute liver injury, a plasmid containing KLF4 was injected via tail veins 48 h prior to CCl 4 treatment.…”

Section: Discussionmentioning

confidence: 99%

Mechanism of KLF4 Protection against Acute Liver Injury via Inhibition of Apelin Signaling

Shi

Shen

et al. 2019

Oxidative Medicine and Cellular Longevity

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Krüppel-like factor 4 (KLF4) is a key transcription factor that regulates genes involved in the proliferation or differentiation in different tissues. Apelin plays roles in cardiovascular functions, metabolic disease, and homeostatic disorder. However, the biological function of apelin in liver disease is still ongoing. In this study, we investigated the mechanism of KLF4-mediated protection against acute liver injury via the inhibition of the apelin signaling pathway. Mice were intraperitoneally injected with carbon tetrachloride (CCl4; 0.2 mL dissolved in 100 mL olive oil, 10 mL/kg) to establish an acute liver injury model. A KLF4 expression plasmid was injected through the tail vein 48 h before CCl4 treatment. In cultured LX-2 cells, pAd-KLF4 or siRNA KLF4 was overexpressed or knockdown, and the mRNA and protein levels of apelin were determined. The results showed that the apelin serum level in the CCl4-injected group was higher than that of control group, and the expression of apelin in the liver tissues was elevated while KLF4 expression was decreased in the CCl4-injected group compared to the KLF4-plasmid-injected group. HE staining revealed serious hepatocellular steatosis in the CCl4-injected mice, and KLF4 alleviated this steatosis in the mice injected with KLF4 plasmid. In vitro experiments showed that tumor necrosis factor-alpha (TNF-α) could downregulate the transcription and translation levels of apelin in LX-2 cells and also upregulate KLF4 mRNA and protein expression. RT-PCR and Western blotting showed that the overexpression of KLF4 markedly decreased basal apelin expression, but knockdown of KLF4 restored apelin expression in TNF-α-treated LX-2 cells. These in vivo and in vitro experiments suggest that KLF4 plays a key role in inhibiting hepatocellular steatosis in acute liver injury, and that its mechanism might be the inhibition of the apelin signaling pathway.

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MircoRNA-145 promotes activation of hepatic stellate cells via targeting krüppel-like factor 4

Cited by 24 publications

References 35 publications

C/EBP Homologous Protein (CHOP) Activates Macrophages and Promotes Liver Fibrosis inSchistosoma japonicum-Infected Mice

C/EBP Homologous Protein (CHOP) Activates Macrophages and Promotes Liver Fibrosis inSchistosoma japonicum-Infected Mice

MicroRNA-145 promotes the epithelial-mesenchymal transition in peritoneal dialysis-associated fibrosis by suppressing fibroblast growth factor 10

Mechanism of KLF4 Protection against Acute Liver Injury via Inhibition of Apelin Signaling

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