Respective roles of the mitogen-activated protein kinase (MAPK) family members in pancreatic stellate cell activation induced by transforming growth factor-β1 (TGF-β1)

Xu, Xichen; Liu, Fang; Xin, Jia‐Qi; Fan, Jingjing; Wu, Nan; Zhu, Lijun; Duan, Li‐Fang; Li, Yongyu; Zhang, Hong

doi:10.1016/j.bbrc.2018.04.176

Cited by 39 publications

(29 citation statements)

References 27 publications

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“…The MAPK signal transduction pathways are amongst the most widespread mechanisms involved in the regulation of eukaryotic cells (47). As shown previously, MAPKs can be activated by TGF-β1 and regulate autophagy (48)(49)(50)(51)(52). In the present study, the role of the most extensively studied MAPK pathways (ERK, p38 and JNK) in TGF-β1-induced autophagy were assessed.…”

Section: Discussionmentioning

confidence: 58%

TGF‑β1‑induced autophagy activates hepatic stellate cells via the ERK and JNK signaling pathways

et al. 2020

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Transforming growth factor β1 (TGF-β1) is one of the most important fibrogenic factors promoting the activation of hepatic stellate cells (HScs). Autophagy is a process used by cells to degrade and recycle cellular proteins. Although TGF-β1 induces autophagy in several other cellular systems, the association between its effect on fibrogenesis and autophagy in HScs have not been determined. Liver tissues from c57BL/6 mice and the mouse HSc line JS1 were analyzed. Acute and chronic liver injury models were induced by carbon tetrachloride (ccl 4), and JS1 cells were stimulated by TGF-β1 to assess the mechanism and relationship between autophagy and fibrosis. Liver tissues from acute and chronic injury models induced by ccl 4 demonstrated evidence of increased autophagic activity, as assessed by the expression of the microtubule-associated protein 1 light chain 3BII protein. TGF-β1 stimulated the activation of JS1 cells and simultaneously increased autophagy flux. However, this effect was attenuated when autophagy was inhibited using chloroquine, 3-methyladenine or lentiviral short hairpin RNA-mediated knockdown of autophagy-related gene 7. Furthermore, whether MAPK, including ERK, JNK and p38 MAPK cascades were associated with TGF-β1-induced autophagy in JS1 cells was determined. Subsequently, it was shown that the ERK inhibitor, Pd98059, and JNK inhibitor, SP600125, were able to reverse TGF-β1-induced autophagy and fibrosis. The results of the present study suggest that TGF-β1-induced autophagy is involved in the activation of JS1 cells, possibly through activation of the ERK and JNK signaling pathways.

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Section: Discussionmentioning

confidence: 58%

TGF‑β1‑induced autophagy activates hepatic stellate cells via the ERK and JNK signaling pathways

et al. 2020

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“…The central members of the MAPKs (ERK, JNK, and p38 MAPK) could transduce signals that are generated by cytokines, growth factors, and intracellular stress. ERK, JNK, and p38 MAPK have been reported increased in mice chronic pancreatitis model, and PSCs were the source of producing MAPKs [17].…”

Section: Mapksmentioning

confidence: 98%

“…It has been observed that increased expression of TGF-β in the injured acinar cells which were adjacent to areas of fibrosis [15]. TGF-β1 could activate MAPKs signal pathway and induce an enhanced mRNA expression level of JNK1 and ERK1, which then leading PSCs to differentiate into myofibroblasts that could secret a variety of ECM, such as type I collagen and fibronectin [16][17][18]. Further studies have demonstrated that PSCs synthesize TGF-β1 itself, which suggesting the possible existence of autocrine loops that may contribute to the continuous activation of PSCs after an initial exogenous signal [19].…”

Section: Tgf-βmentioning

confidence: 99%

“…Studies of knockout mice have shown that MAPK phosphatase (MKP) plays a negative regulatory role in JNK pathway, and the use of reactive oxygen species (ROS) to inhibit MKP activity can prolong the activation of JNK [100]. Moreover, JNK and ERK were believed respond directly to TGF-β1 and PDGF, which are considered as the most important factors of PSCs proliferation and ECM deposition [17,46]. p38, a kind of stress-activated protease (SAPK), is activated by a variety of proinflammatory-related factors, and takes an effect on apoptosis, transcriptional regulation, cytokine production and cytoskeleton recognition [101].…”

Section: Mapksmentioning

confidence: 99%

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Molecular Mechanism of Pancreatic Stellate Cells Activation in Chronic Pancreatitis and Pancreatic Cancer

Jin¹,

Hong²,

Guo³

et al. 2020

J. Cancer

103

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Activated pancreatic stellate cells (PSCs) are the main effector cells in the process of fibrosis, a major pathological feature in pancreatic diseases that including chronic pancreatitis and pancreatic cancer. During tumorigenesis, quiescent PSCs change into an active myofibroblast-like phenotype which could create a favorable tumor microenvironment and facilitate cancer progression by increasing proliferation, invasiveness and inducing treatment resistance of pancreatic cancer cells. Many cellular signals are revealed contributing to the activation of PSCs, such as transforming growth factor-β, platelet derived growth factor, mitogen-activated protein kinase (MAPK), Smads, nuclear factor-κB (NF-κB) pathways and so on. Therefore, investigating the role of these factors and signaling pathways in PSCs activation will promote the development of PSCs-specific therapeutic strategies that may provide novel options for pancreatic cancer therapy. In this review, we systematically summarize the current knowledge about PSCs activation-associated stimulating factors and signaling pathways and hope to provide new strategies for the treatment of pancreatic diseases.

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“…TGF-β is a special growth factor and at the same time is chemotactic for fibroblasts, stimulates fibroblast proliferation, and increases the synthesis of a number of extracellular matrix proteins [13,14]. It promotes the initiation and progression of pancreatic fibrosis through matrix production and growth control of the pancreatic stellate cells in vitro [15][16][17]. The Smads are a family of intracellular regulatory proteins that act downstream of the TGF-β Type I receptor.…”

Section: Introductionmentioning

confidence: 99%

HDAC inhibitors promote pancreatic stellate cell apoptosis and relieve pancreatic fibrosis by upregulating miR-15/16 in chronic pancreatitis

Feng

Xiangcheng

et al. 2020

Human Cell

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In chronic pancreatitis, PSCs are activated by proinflammatory cytokines to induce pancreatic fibrogenesis. HDAC inhibition protected against the pancreatic fibrosis and the apoptosis of PSCs through induced apoptosis and depressed inflammation. In our study, we found that miR-15 and miR-16 decreased significantly in chronic pancreatitis and HDAC inhibition could recover the levels of these two miRNAs. HDAC regulated the transcription of miR-15 and miR-16, which then modulate the apoptosis and fibrosis of PSCs. And we proved that Bcl-2 and Smad5 were the target genes of miR-15 and miR-16, which illustrated how HDAC inhibition alleviated the apoptosis and fibrogenesis of PSCs in chronic pancreatitis. These results suggested that HDAC inhibition protects against CP by promoting apoptosis and TGF-β/Smads signaling pathways, and indicated that HDAC inhibition is a potential therapy to alleviate CP patients in clinic, and these need to be explored further.

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Respective roles of the mitogen-activated protein kinase (MAPK) family members in pancreatic stellate cell activation induced by transforming growth factor-β1 (TGF-β1)

Cited by 39 publications

References 27 publications

TGF‑β1‑induced autophagy activates hepatic stellate cells via the ERK and JNK signaling pathways

TGF‑β1‑induced autophagy activates hepatic stellate cells via the ERK and JNK signaling pathways

Molecular Mechanism of Pancreatic Stellate Cells Activation in Chronic Pancreatitis and Pancreatic Cancer

HDAC inhibitors promote pancreatic stellate cell apoptosis and relieve pancreatic fibrosis by upregulating miR-15/16 in chronic pancreatitis

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