Galectin-1 expression in activated pancreatic satellite cells promotes fibrosis in chronic pancreatitis/pancreatic cancer via the TGF-β1/Smad pathway

Tang, Dong; Qi, Weier; Zhang, Jingqiu; Zhang, Hongpeng; Zhou, Yuan; Xu, Jiaming; Yan, Chong; Huang, Yuqin; Xiong, Qiyan; Wang, Sen; Tian, Ying; Lu, Yongdie; Ge, Xin; Shen, Wenjing; Wang, Daorong

doi:10.3892/or.2018.6202

Cited by 36 publications

(43 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Subretinal fibrosis is a serious complication associated with CNV, leading to permanent vision loss in neovascular AMD (4, 6, 7, 13). Galectin-1 was shown to enhance the TGF-b-SMAD pathway, thus leading to the development of pulmonary and pancreatic fibrosis (19,20). To evaluate the lesion area of CNV-associated fibrotic tissues, composed mainly of type I collagen, we labeled flat mounts of the RPE-choroid complex with anti-type I collagen antibody at postlaser d 7 (Fig.…”

Section: Lgals1 Deficiency Suppresses Cnv-associated Subretinal Fibromentioning

confidence: 99%

“…In addition to angiogenesis, galectin-1 has also been reported to be involved in mesenchymal activity via SMAD2 signaling in various cells, including gastric cancer cells, pancreatic stellate cells, and fibroblasts (19)(20)(21). Galectin-1 induced the phosphorylation of SMAD2 through its molecular interaction with SMAD2 in lung fibroblasts (19), thus promoting pulmonary fibrosis (19,22).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Galectin‐1 promotes choroidal neovascularization and subretinal fibrosis mediatedviaepithelialmesenchymal transition

Kanda

Liu

et al. 2018

FASEB j.

View full text Add to dashboard Cite

VEGFA and TGF‐β are known major angiogenic and fibrogenic factors. Galectin‐1, encoded by lectin, galactoside‐binding, soluble (LGALS)1, has attracted growing attention for its facilitatory role in angiogenesis and fibrosis through its modification of VEGFA and TGF‐β receptor signaling pathways. We reveal galectin‐1 involvement in the mouse model of laser‐induced choroidal neovascularization (CNV) and subretinal fibrosis, both of which represent the pathogenesis of age‐related macular degeneration (AMD). Neither deletion nor overexpression of Lgals1 affected physiologic retinal development or visual function. Galectin‐1/Lgals1 was upregulated by CNV induction, whereas deletion of Lgals1 suppressed CNV together with downstream molecules of VEGF receptor (VEGFR)2. Loss of Lgals1 also attenuated subretinal fibrosis, expression of epithelial‐mesenchymal transition (EMT) markers including Snai1, and phosphorylation of SMAD family member 2. Supporting these in vivo findings, silencing of LGALS1 in human retinal pigment epithelial (RPE) cells inhibited TGF‐β1‐induced EMT‐related molecules and cell motilities. Conversely, overexpression of Lgals1 enhanced CNV and subretinal fibrosis. Specimens from patients with AMD demonstrated colocalization of galectin‐1 with VEGFR2 in neovascular endothelial cells and with phosphorylated SMAD2 in RPE cells. These results suggested a biologic significance of galectin‐1 as a key promotor for both angiogenesis and fibrosis in eyes with AMD.—Wu, D., Kanda, A., Liu, Y., Kase, S., Noda, K., Ishida, S. Galectin‐1 promotes choroidal neovascularization and subretinal fibrosis mediated via epithelialmesenchymal transition. FASEB J. 33, 2498–2513 (2019). http://www.fasebj.org

show abstract

Section: Lgals1 Deficiency Suppresses Cnv-associated Subretinal Fibromentioning

confidence: 99%

mentioning

confidence: 99%

Galectin‐1 promotes choroidal neovascularization and subretinal fibrosis mediatedviaepithelialmesenchymal transition

Kanda

Liu

et al. 2018

FASEB j.

View full text Add to dashboard Cite

show abstract

“…MMPs and TIMPs are produced by hepatocytes in early stage of liver injury . TGF‐β1 mediates the balance of MMPs/TIMPs through Smad‐dependent pathway . Moreover, retinoic acid destructs MMP9/TIMP1 balance via the activated TGF‐β/Smad pathway, which disturbs ECM formation …”

Section: Introductionmentioning

confidence: 99%

“…37 TGF-β1 mediates the balance of MMPs/TIMPs through Smaddependent pathway. 38 Moreover, retinoic acid destructs MMP9/TIMP1 balance via the activated TGF-β/Smad pathway, which disturbs ECM formation. 39 According to the researches above, we hypothesized that Nano NiO could induce hepatic fibrosis, which might be related to TGF-β1-mediated Smad and MAPK pathways and EMT occurrence in vivo and in vitro.…”

mentioning

confidence: 99%

TGF‐β1 mediated Smad signaling pathway and EMT in hepatic fibrosis induced by Nano NiO in vivo and in vitro

Zhang

Chang

Wang

et al. 2019

Environmental Toxicology

View full text Add to dashboard Cite

Nickel oxide nanoparticles (Nano NiO) bears hepatotoxicity, while whether it leads to liver fibrosis remains unclear. The aim of this study was to establish the Nano NiO‐induced hepatic fibrosis model in vivo and investigate the roles of transforming growth factor β1 (TGF‐β1) in Smad pathway activation, epithelial‐mesenchymal transition (EMT) occurrence, and extracellular matrix (ECM) deposition in vitro. Male Wistar rats were exposed to 0.015, 0.06, and 0.24 mg/kg Nano NiO by intratracheal instilling twice a week for 9 weeks. HepG2 cells were treated with 100 μg/mL Nano NiO and TGF‐β1 inhibitor (SB431542) to explore the mechanism of collagen formation. Results of Masson staining as well as the elevated levels of type I collagen (Col‐I) and Col‐III suggested that Nano NiO resulted in hepatic fibrosis in rats. Furthermore, Nano NiO increased the protein expression of TGF‐β1, p‐Smad2, p‐Smad3, alpha‐smooth muscle actin (α‐SMA), matrix metalloproteinase9 (MMP9), and tissue inhibitors of metalloproteinase1 (TIMP1), while decreased the protein content of E‐cadherin and Smad7 in rat liver and HepG2 cells. Most importantly, Nano NiO‐triggered the abnormal expression of the abovementioned proteins were all alleviated by co‐treatment with SB431542, implying that TGF‐β1‐mediated Smad pathway, EMT and MMP9/TIMP1 imbalance were involved in overproduction of collagen in HepG2 cells. In conclusion, these findings indicated that Nano NiO induced hepatic fibrosis via TGF‐β1‐mediated Smad pathway activation, EMT occurrence, and ECM deposition.

show abstract

“…9,10 Therefore, activation of PSCs is considered a core event in pancreatic fibrosis. 11,12 Epithelial mesenchymal transition (EMT) is a biological phenomenon in which epithelial cells lose epithelial properties to obtain stromal cell phenotypes. Recent studies confirmed the role of EMT in fibrosis of organs such as the lungs and the liver.…”

Section: Introductionmentioning

confidence: 99%

Hic‐5 deficiency protects cerulein‐induced chronic pancreatitis via down‐regulation of the NF‐κB (p65)/IL‐6 signalling pathway

Chen

Tan

Qian

et al. 2019

J Cellular Molecular Medi

View full text Add to dashboard Cite

Chronic pancreatitis (CP), characterized by pancreatic fibrosis, is a recurrent, progressive and irreversible disease. Activation of the pancreatic stellate cells (PSCs) is considered a core event in pancreatic fibrosis. In this study, we investigated the role of hydrogen peroxide-inducible clone-5 (Hic-5) in CP. Analysis of the human pancreatic tissue samples revealed that Hic-5 was overexpressed in patients with CP and was extremely low in healthy pancreas. Hic-5 was significant up-regulated in the activated primary PSCs independently from transforming growth factor beta stimulation. CP induced by cerulein injection was ameliorated in Hic-5 knockout (KO) mice, as shown by staining of tissue level. Simultaneously, the activation ability of the primary PSCs from Hic-5 KO mice was significantly attenuated. We also found that the Hic-5 up-regulation by cerulein activated the NF-κB (p65)/IL-6 signalling pathway and regulated the downstream extracellular matrix (ECM) genes such as α-SMA and Col1a1. Therefore, we determined whether suppressing NF-κB/p65 alleviated CP by treating mice with the NF-κB/p65 inhibitor triptolide in the cerulein-induced CP model and found that pancreatic fibrosis was alleviated by NF-κB/p65 inhibition.These findings provide evidence for Hic-5 as a therapeutic target that plays a crucial role in regulating PSCs activation and pancreatic fibrosis. K E Y W O R D S chronic pancreatitis, Hic-5, NF-κB, pancreatic stellate cells, triptolide | 1489 CHEN Et al. S U PP O RTI N G I N FO R M ATI O N Additional supporting information may be found online in the Supporting Information section. How to cite this article: Chen H, Tan P, Qian B, et al. Hic-5 deficiency protects cerulein-induced chronic pancreatitis via down-regulation of the NF-κB (p65)/IL-6 signalling pathway.

show abstract

Galectin-1 expression in activated pancreatic satellite cells promotes fibrosis in chronic pancreatitis/pancreatic cancer via the TGF-β1/Smad pathway

Cited by 36 publications

References 28 publications

Galectin‐1 promotes choroidal neovascularization and subretinal fibrosis mediatedviaepithelialmesenchymal transition

Galectin‐1 promotes choroidal neovascularization and subretinal fibrosis mediatedviaepithelialmesenchymal transition

TGF‐β1 mediated Smad signaling pathway and EMT in hepatic fibrosis induced by Nano NiO in vivo and in vitro

Hic‐5 deficiency protects cerulein‐induced chronic pancreatitis via down‐regulation of the NF‐κB (p65)/IL‐6 signalling pathway

Contact Info

Product

Resources

About