TLR2 mediates autophagy through ERK signaling pathway in Mycoplasma gallisepticum -infected RAW264.7 cells

Lu, Zhaoqing; Xie, Daoyuan; Chen, Ying; Tian, E; Ishfaq, Muhammad; Chen, Xueping; Miao, Yusong; Hu, Wusheng; Wu, Ziyong; Ni, Huili; Xin, Jiuqing; Li, Yuan; Li, Jichang

doi:10.1016/j.molimm.2017.04.013

Cited by 58 publications

(45 citation statements)

References 34 publications

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“…ERK mediated various physiological functions, including proliferation and autophagy 51‐53 . However, the current study showed that ATG regulates ERK phosphorylation.…”

Section: Discussioncontrasting

confidence: 57%

Trehalose reduces bone loss in experimental biliary cirrhosis rats via ERK phosphorylation regulation by enhancing autophagosome formation

Wang

et al. 2020

FASEB j.

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Bone loss is a severe complication of primary biliary cirrhosis (PBC). Trehalose was intermittently administered in bile duct‐ligated (BDL) male rats, a PBC‐related osteoporosis model, for 4 weeks to reduce osteoporosis. Femoral bones were assessed ex vivo by micro computed tomography (CT) and histomorphometry. The potential mechanisms related to the reduction of osteoporosis were explored by evaluating the effect of trehalose on osteoblast autophagy, osteogenesis, osteoclastogenesis, and ERK phosphorylation. The results demonstrated that trehalose reduced osteoporosis of BDL rats and decreased osteoblast‐mediated osteoclast differentiation by enhancing osteoblast autophagy to regulate osteoprotegerin (OPG) secretion. Hydroxychloroquine (HCQ) increased the expression of OPG and OPG/receptor activator genes for nuclear factor‐κB ligand (RANKL) ratio, and reduced osteoblast‐mediated osteoclastogenesis by inhibiting autophagy flux and inducing autophagosome formation. Furthermore, trehalose increased the phosphorylation of ERK1/2 in MC3T3‐E1 cells, and the ERK inhibitor PD98059 reversed the upregulation of OPG gene and reduction of trehalose‐induced osteoclastogeneis. The treatment with HCQ markedly increased the ERK phosphorylation. The correlation between autophagosome formation and ERK phosphorylation was confirmed in autophagy proteins (ATG) 4B or ATG5‐deficient cells. Thus, trehalose could decrease osteoblast‐mediated osteoclastogenesis and reduce PBC‐related bone loss by regulating ERK phosphorylation via autophagosome formation.

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“…ERK mediated various physiological functions, including proliferation and autophagy 51‐53 . However, the current study showed that ATG regulates ERK phosphorylation.…”

Section: Discussioncontrasting

confidence: 57%

Trehalose reduces bone loss in experimental biliary cirrhosis rats via ERK phosphorylation regulation by enhancing autophagosome formation

Wang

et al. 2020

FASEB j.

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“…Substantial evidence has demonstrated that p38 and ERK play important roles in regulating autophagy in the areas of acute or chronic tissue injury20, 21 To explore the mechanisms of cell autophagy responsible for the TAK1 signal pathway during cisplatin‐induced AKI, we examined whether TAK1 inhibition affects the phosphorylation of p38 and ERK. Our result showed that cisplatin‐induced AKI increased phosphorylation of p38 and ERK, as detected by Western blotting in kidneys of control group mice.…”

Section: Resultsmentioning

confidence: 99%

“…Inhibition of TAK1 decreases phosphorylation of p38 and ERK in kidneys of mice with cisplatininduced AKI p38 and ERK are two main subfamilies of mammalian MAPKs, which are a group of serine/threonine-specific protein kinases generally expressed in all cell types and are essential components of signal transduction in various physiological and pathological processes 19. Substantial evidence has demonstrated that p38 and ERK play important roles in regulating autophagy in the areas of acute or chronic tissue injury20,21 To explore the mechanisms of cell autophagy responsible for the TAK1 signal pathway during cisplatin-induced AKI, we examined whether TAK1 inhibition affects the phosphorylation of p38 and ERK. Our result showed that cisplatin-induced AKI increased phosphorylation of p38 and ERK, as detected by Western blotting in kidneys of control group mice.…”

mentioning

confidence: 99%

TAK1 mediates excessive autophagy via p38 and ERK in cisplatin‐induced acute kidney injury

Zhou

Fan

Zhong

et al. 2018

J Cellular Molecular Medi

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The ability of cisplatin (cis‐diamminedichloroplatinum II) toxicity to induce acute kidney injury (AKI) has attracted people's attention and concern for a long time, but its molecular mechanisms are still widely unknown. We found that the expression of transforming growth factor‐β (TGF‐β)‐activated kinase 1 (TAK1) could be increased in kidneys of mice administrated with cisplatin. Autophagy is an evolutionarily conserved catabolic pathway and is involved in various acute and chronic injuries. Moreover, p38 MAPK (mitogen‐activated protein kinase) and ERK regulate autophagy in response to various stimuli. Therefore, our hypothesis is that cisplatin activates TAK1, which phosphorylates p38 and ERK, leading to excessive autophagy of tubular epithelial cells and thus exacerbating kidney damage. Here, BALB/c mice were intraperitoneally injected with a TAK1 inhibitor and were then administrated with sham or cisplatin at 20 mg/kg by intraperitoneal injection. Compared with mice in the vehicle cisplatin group, mice intraperitoneally injected with a TAK1 inhibitor were found to have lower serum creatinine and less tubular damage following cisplatin‐induced AKI. Furthermore, inhibition of TAK1 reduced p38 and Erk phosphorylation, decreased expression of LC3II and reversed the down‐regulation of P62 expression induced by cisplatin. The hypothesis was verified with tubular epithelial cells administrated with cisplatin in vitro. Finally, p38 inhibitor or ERK inhibitor abated autophagy activation and cell viability reduction in tubular epithelial cells treated with cisplatin plus TAK1 overexpression vector. Taken together, our results show that cisplatin activates TAK1, which phosphorylates p38 and ERK, leading to excessive autophagy of tubular epithelial cells that exacerbates kidney damage.

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“…In its recognition of A. fumigatus, TLR2 serves a critical role in autophagy-induction in infected macrophages (14). In RAW264.7 cells, this induction is reached by activating multiple signaling pathways, including the JNK, ERK, and PI3K signaling pathways (29)(30)(31). Although the fungus used in these studies was not A. fumigatus, the same pathways were suggested to contribute to the autophagy in macrophages induced by A. fumigatus.…”

Section: Discussionmentioning

confidence: 85%

miRNA‑344b‑1‑3p modulates the autophagy of NR8383 cells during Aspergillus�fumigatus infection via TLR2

et al. 2019

Exp Ther Med

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Autophagy serves a pivotal role in host defense during fungal infections, and the contribution by toll-like receptor 2 (TLR2) has been well demonstrated. It has been reported that microRNA-344a-1-3p (miR-344a-1-3p) can directly target TLR2. However, the expression of TLR2 significantly decreases during Aspergillus fumigatus infection. Therefore, the specific role of miR-344a-1-3p in the host defense against A. fumigatus infection remains to be elucidated. In the present study, A. fumigatus infection increased the expression of TLR2 and induced autophagy, which was indicated by increasing expression levels of autophagy-related protein 5 (ATG5), Beclin-1, light chain 3 (LC3)-1 and LC3-II, as measured by western blot analysis, and an increased number of GFP-LC3 puncta, as measured by fluorescence. Following transfection with miR-344a-1-3p mimics and/or TLR2, miR-344b-1-3p significantly inhibited the expression of TLR2, Beclin-1, ATG5, LC3-I and LC3-II, whereas the overexpression of TLR2 significantly attenuated the inhibitory effect on autophagy by miR-344b-1-3p. Collectively, these findings demonstrate that A. fumigatus can be controlled by the induction of autophagy following de-repression of the expression of TLR2, mediated by miR-344a-1-3p.

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TLR2 mediates autophagy through ERK signaling pathway in Mycoplasma gallisepticum -infected RAW264.7 cells

Cited by 58 publications

References 34 publications

Trehalose reduces bone loss in experimental biliary cirrhosis rats via ERK phosphorylation regulation by enhancing autophagosome formation

Trehalose reduces bone loss in experimental biliary cirrhosis rats via ERK phosphorylation regulation by enhancing autophagosome formation

TAK1 mediates excessive autophagy via p38 and ERK in cisplatin‐induced acute kidney injury

miRNA‑344b‑1‑3p modulates the autophagy of NR8383 cells during Aspergillus�fumigatus infection via TLR2

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