Lipopolysaccharide enhances <scp>TGF</scp>‐β1 signalling pathway and rat pancreatic fibrosis

Sun, Li; Xiu, Ming; Wang, Shuhua; Brigstock, David R.; Li, Hongyan; Qu, Limei; Gao, Runping

doi:10.1111/jcmm.13526

Cited by 47 publications

(21 citation statements)

References 36 publications

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“…TGF-β is one of the strongest fibrogenic cytokines, and it is involved in the fibrogenesis of many diseases ( Meng et al, 2016 ; Kim et al, 2018 ; Ma and Meng, 2019 ). During CP progression, upregulation of TGF-β in the pancreas further activates PSCs, promotes the synthesis of the ECM, and accelerates pancreatic fibrosis ( Liu P. et al, 2019 ; Sun et al, 2018 ; Xu et al, 2018 ). To explore the detailed mechanism of baicalin inhibiting PSC activation, we further isolated the primary PSCs of mice, cultured them to the second generation, and stimulated them with TGF-β1.…”

Section: Discussionmentioning

confidence: 99%

“…Many experiments have demonstrated that the activation of pancreatic stellate cells (PSCs) and subsequent production of extracellular matrix (ECM) play critical roles in the progression of pancreatic fibrosis in CP ( Bynigeri et al, 2017 ; Li et al, 2018 ). PSCs remains quiescent under physiological conditions, but they are activated once the pancreas is exposed to various damage factors, especially the inflammatory factors released by the local infiltrated inflammatory cells in the microenvironment of the pancreas ( Sun et al, 2018 ; Xue et al, 2018 ). However, whether baicalin interferes with the activation of PSCs, as well as its detailed molecular mechanism, remains unknown.…”

Section: Introductionmentioning

confidence: 99%

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Baicalin Ameliorates Pancreatic Fibrosis by Inhibiting the Activation of Pancreatic Stellate Cells in Mice with Chronic Pancreatitis

Fan

Duan

et al. 2021

Front. Pharmacol.

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Pancreatic inflammation and fibrosis are typical pathological features in chronic pancreatitis (CP). Activated pancreatic stellate cells (PSCs) have been regarded as the core event in the development of pancreatic fibrosis and are considered to be the key target for treatment of CP. Baicalin (C21H18O11), the main chemical composition of Baikal skullcap in the traditional Chinese medicines Dachaihu decoction (DCHD) and Xiaochaihu decoction (XCHD), has shown significant effects in the treatment of pancreatic fibrosis in CP mice; however, whether baicalin can inhibit the activation of PSCs and its underlying mechanism remain unclear. In this study, the influence of baicalin on activated PSCs in vitro and in vivo was investigated, and the results showed that Baicalin could significantly ameliorate the degree of pancreatic inflammation and fibrosis, while decreasing the levels of alpha-smooth muscle actin (α-SMA), F4/80 (surface markers of mouse macrophages), nuclear factor kappa-B (NF-κB), monocyte chemotactic protein 1 (MCP-1), and collagen type I alpha 1 (COL1A1)in the pancreas. Moreover, NF-κB and α-SMA were co-expressed in the pancreas of CP mice. Baicalin treatment markedly reduced the expression of co-location of α-SMA and NF-κB. In vitro, the protein expression levels of transforming growth factor-β receptor 1 (TGF-βR1), phosphorylated TGF-β activated kinase 1 p-TAK 1, and NF-κBp65 in PSCs were all remarkably reduced after treatment with baicalin. In addition, baicalin could inhibit MCP-1 mRNA expression in supernatant of activated PSCs, as well as the excessive migration of macrophages. Taken together, our findings indicated that baicalin could inhibit the TGF-β1/TGF-βR1/TAK1/NF-κB signaling pathway of activated PSCs, reduce the secretion of MCP-1, and further decrease the infiltration of macrophages and inflammation cells of the local microenvironment of the pancreas. Thus, this study provides a reliable experimental basis for baicalin in the prevention and treatment of CP.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Baicalin Ameliorates Pancreatic Fibrosis by Inhibiting the Activation of Pancreatic Stellate Cells in Mice with Chronic Pancreatitis

Fan

Duan

et al. 2021

Front. Pharmacol.

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“…In this work we discovered that in cancer cells expressing TLR4, HMGB1 can induce TGF-b production and secretion (Figure 1). Interestingly, TLR4 has recently been shown to mediate TGF-b production when activated by lipopolysaccharide (LPS), its pathogen-associated ligand, and some endogenous stimuli such as hyaluronic acid (25,26). It was also demonstrated that HMGB1-induced activation of TGF-b production in TLR4expressing cells takes place through the activator protein 1 (AP-1) transcription factor and its upstream pathway (9).…”

Section: Discussionmentioning

confidence: 99%

High Mobility Group Box 1 (HMGB1) Induces Toll-Like Receptor 4-Mediated Production of the Immunosuppressive Protein Galectin-9 in Human Cancer Cells

et al. 2021

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High mobility group box 1 (HMGB1) is a non-histone protein which is predominantly localised in the cell nucleus. However, stressed, dying, injured or dead cells can release this protein into the extracellular matrix passively. In addition, HMGB1 release was observed in cancer and immune cells where this process can be triggered by various endogenous as well as exogenous stimuli. Importantly, released HMGB1 acts as a so-called “danger signal” and could impact on the ability of cancer cells to escape host immune surveillance. However, the molecular mechanisms underlying the functional role of HMGB1 in determining the capability of human cancer cells to evade immune attack remain unclear. Here we report that the involvement of HMGB1 in anti-cancer immune evasion is determined by Toll-like receptor (TLR) 4, which recognises HMGB1 as a ligand. We found that HGMB1 induces TLR4-mediated production of transforming growth factor beta type 1 (TGF-β), displaying autocrine/paracrine activities. TGF-β induces production of the immunosuppressive protein galectin-9 in cancer cells. In TLR4-positive cancer cells, HMGB1 triggers the formation of an autocrine loop which induces galectin-9 expression. In malignant cells lacking TLR4, the same effect could be triggered by HMGB1 indirectly through TLR4-expressing myeloid cells present in the tumour microenvironment (e. g. tumour-associated macrophages).

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“…TGF-β1 is a member of TGF-beta superfamily, which plays a role in several biological processes [19]. It has been uncovered that TGF-β1 is a key regulator of PSC activation and ECM production [20]. A previous study revealed that TGF-β1 overexpression induced CP in murine pancreas [21].…”

Section: Discussionmentioning

confidence: 99%

TGF-β1 induced proliferation, migration, and ECM accumulation through the SNHG11/miR-34b/LIF pathway in human pancreatic stellate cells

Guo

et al. 2021

Endocr J

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Chronic pancreatitis (CP) is a chronic inflammatory and fibrotic disease of the pancreas, and activated pancreatic stellate cells (PSCs) play a vital role in the progression of pancreatic fibrosis in CP. It has been reported that long non-coding RNA small nucleolar RNA host gene 11 (SNHG11) is highly expressed in chronic pancreatitis (CP) patients. However, the role of SNHG11 in CP progression is unclear. The purport of the study was to survey the role of SNHG11 in CP. We employed transforming growth factor (TGF)-beta1 (TGF-β1) to activate human pancreatic stellate cells (PSCs). Expression of SNHG11 was assessed with qRT-PCR. Loss-of-function experiments were executed to evaluate the effects of SNHG11 on the proliferation and migration of TGF-β1-treated PSCs. Some protein levels were detected by western blotting. The regulatory mechanism of SNHG11 was verified by the dual-luciferase reporter and RIP assays. As a result, SNHG11 was upregulated in plasma of CP patients and TGF-β1-treated PSCs. Also, SNHG11 inhibition reduced TGF-β1-induced proliferation, migration, and ECM accumulation in PSCs. Mechanistically, SNHG11 regulated leukemia inhibitory factor (LIF) expression by sponging miR-34b. Furthermore, miR-34b inhibitor abolished SNHG11 silencing-mediated effects on TGF-β1-treated PSC proliferation, migration, and ECM accumulation. LIF overexpression counteracted the repressive influence of miR-34b mimic on proliferation, migration, and ECM accumulation of TGF-β1-treated PSCs. In conclusion, SNHG11 knockdown reduced TGF-β1-induced PSC proliferation, migration, and ECM accumulation by the miR-34b/LIF axis.

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Lipopolysaccharide enhances TGF‐β1 signalling pathway and rat pancreatic fibrosis

Cited by 47 publications

References 36 publications

Baicalin Ameliorates Pancreatic Fibrosis by Inhibiting the Activation of Pancreatic Stellate Cells in Mice with Chronic Pancreatitis

Baicalin Ameliorates Pancreatic Fibrosis by Inhibiting the Activation of Pancreatic Stellate Cells in Mice with Chronic Pancreatitis

High Mobility Group Box 1 (HMGB1) Induces Toll-Like Receptor 4-Mediated Production of the Immunosuppressive Protein Galectin-9 in Human Cancer Cells

TGF-β1 induced proliferation, migration, and ECM accumulation through the SNHG11/miR-34b/LIF pathway in human pancreatic stellate cells

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