Engeletin ameliorates pulmonary fibrosis through endoplasmic reticulum stress depending on lnc949-mediated TGF-β1-Smad2/3 and JNK signalling pathways

Zhang, Jinjin; Chen, Xiaoqing; Chen, Hongbin; Li, Rongrong; Xu, Pan; Lv, Changjun; Liu, Bo; Song, Xiaodong

doi:10.1080/13880209.2020.1834590

Cited by 16 publications

(11 citation statements)

References 35 publications

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“…ATF4 is a basic leucine zipper transcription factor best known to be induced by stress responses. ATF4 has long been considered a profibrotic molecule because it enhances fibroblast proliferation, collagen synthesis, migration, and differentiation to myofibroblasts and induces fibroblasts’ apoptosis in tissue fibrosis [ 30 , 31 , 32 , 33 ]. Despite being less studied in lung disease, ATF4 was a profibrotic role in lung fibroblast activation and renal tubulointerstitial fibrosis [ 29 , 30 ].…”

Section: Discussionmentioning

confidence: 99%

TRIB3 Mediates Fibroblast Activation and Fibrosis though Interaction with ATF4 in IPF

Wang

Zhao

Xia

et al. 2022

IJMS

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Idiopathic pulmonary fibrosis (IPF) is a fatal interstitial lung disease characterized by fibroblast activation, excessive deposition of extracellular matrix, and progressive scarring; the pathogenesis remains elusive. The present study explored the role of Tribbles pseudokinase 3 (TRIB3), a well-known stress and metabolic sensor, in IPF. TRIB3 is down-regulated in the lungs of IPF patients in comparison to control subjects. Deficiency of TRIB3 markedly inhibited A549 epithelial cells’ proliferation and migration, significantly reducing wound healing. Conversely, overexpression of TRIB3 promoted A549 cell proliferation and transmigration while it inhibited its apoptosis. Meanwhile, overexpressed TRIB3 inhibited fibroblast activation and decreased ECM synthesis and deposition in MRC5 cells. TRIB3 attenuated pulmonary fibrosis by negative regulation of ATF4, while TRIB3 expression markedly inhibited ATF4 promoter-driven transcription activity and down-regulated ATF4 expression. A co-culture system showed that TRIB3 is important to maintain the normal epithelial–mesenchymal crosstalk and regulate fibroblast activation. Taken together, our data suggested that an axis of TRIB3‒ATF4 is a key mediator in IPF which might be a potential target for fibroproliferative lung disease treatment.

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Section: Discussionmentioning

confidence: 99%

TRIB3 Mediates Fibroblast Activation and Fibrosis though Interaction with ATF4 in IPF

Wang

Zhao

Xia

et al. 2022

IJMS

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“…We found that the oral dosage range of engeletin for diabetes stroke is 25–1000 mg, preferably 25–500 mg. Emerging reports suggest strong neuroprotective properties of engeletin against multiple diseases, namely, brain stroke, pulmonary fibrosis and Alzheimer's disease 17,18 . Given that inflammatory stress contributes to IS‐induced brain injury, and that engeletin is reported as a robust anti‐inflammatory agent, it is possible that engeletin may be novel therapeutic approach for cerebral ischemia pretreatment.…”

Section: Introductionmentioning

confidence: 99%

Engeletin alleviates cerebral ischemia reperfusion‐induced neuroinflammation via the HMGB1/TLR4/NF‐κB network

Zhang

Gao

et al. 2023

J Cellular Molecular Medi

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High-mobility group box1 (HMGB1) induces inflammatory injury, and emerging reports suggest that it is critical for brain ischemia reperfusion. Engeletin, a natural Smilax glabra rhizomilax derivative, is reported to possess anti-inflammatory activity.Herein, we examined the mechanism of engeletin-mediated neuroprotection in rats having transient middle cerebral artery occlusion (tMCAO) against cerebral ischemia reperfusion injury. Male SD rats were induced using a 1.5 h tMCAO, following by reperfusion for 22.5 h. Engeletin (15, 30 or 60 mg/kg) was intravenously administered immediately following 0.5 h of ischemia. Based on our results, engeletin, in a dosedependent fashion, reduced neurological deficits, infarct size, histopathological alterations, brain edema and inflammatory factors, namely, circulating IL-1β, TNFα, IL-6 and IFNγ. Furthermore, engeletin treatment markedly reduced neuronal apoptosis, which, in turn, elevated Bcl-2 protein levels, while suppressing Bax and Cleaved Caspase-3 protein levels. Meanwhile, engeletin significantly reduces overall expressions of HMGB1, TLR4, and NF-κB and attenuated nuclear transfer of nuclear factor kappa B (NF-κB) p65 in ischemic cortical tissue. In conclusion, engeletin strongly prevents focal cerebral ischemia via suppression of the HMGB1/TLR4/NF-κB inflammatory network.

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“…Thus, it is urgent to reveal reagents that can relieve the neurological injury caused by SEV. It is reported that engeletin is closely associated with various pathological processes, such as pulmonary fibrosis, 32 cervical carcinogenesis, 33 and endometritis 34 . Interestingly, Liu et al .…”

Section: Discussionmentioning

confidence: 99%

Engeletin ameliorates sevoflurane‐induced cognitive impairment by activating PPAR‐gamma in neonatal mice

Ying

Wang

2023

Neuropathology

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Sevoflurane (SEV) is a commonly used anesthetic in pediatric surgery. Recent studies reported that repeated use of SEV contributes to cognitive impairment. Engeletin has been discovered to exert anti‐inflammatory effects in various diseases. However, the detailed roles and mechanisms of engeletin in SEV‐induced cognitive dysfunction of neonatal mice remain unclear. In this study, C57BL/6 neonatal mice were randomly divided into Ctrl, SEV, SEV + Engeletin (10 mg /kg), SEV + Engeletin (20 mg/kg), and SEV + Engeletin (40 mg/kg) groups. The Morris water maze (MWM) test suggested that engeletin treatment significantly improved SEV‐induced cognitive impairment in neonatal mice. Employing ELISA and Nissl staining analysis, engeletin reduced neuroinflammation and loss of nerve cells caused by SEV, respectively. The treatment of engeletin dramatically suppressed the activation of microglia and apoptosis induced by SEV in the hippocampus of neonatal mice. Furthermore, the inhibition of PPAR‐γ obviously reversed the abovementioned effects of engeletin in the hippocampus of newborn mice. In conclusion, this study verified that engeletin notably ameliorated SEV‐induced cognitive deficiencies in neonatal mice at least partially by mediating the expression of PPAR‐γ.

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Engeletin ameliorates pulmonary fibrosis through endoplasmic reticulum stress depending on lnc949-mediated TGF-β1-Smad2/3 and JNK signalling pathways

Cited by 16 publications

References 35 publications

TRIB3 Mediates Fibroblast Activation and Fibrosis though Interaction with ATF4 in IPF

TRIB3 Mediates Fibroblast Activation and Fibrosis though Interaction with ATF4 in IPF

Engeletin alleviates cerebral ischemia reperfusion‐induced neuroinflammation via the HMGB1/TLR4/NF‐κB network

Engeletin ameliorates sevoflurane‐induced cognitive impairment by activating PPAR‐gamma in neonatal mice

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