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

Wu, Desheng; Guo, J.; Qi, Benquan; Xiao, Hang

doi:10.1507/endocrj.ej21-0176

Cited by 13 publications

(5 citation statements)

References 35 publications

(27 reference statements)

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“…Furthermore, recent studies showed that multiple miRs (miR-301, miR-200c, miR-149, miR-139, miR-34b) can affect the activity of PSCs during chronic pancreatitis, and modulation of their levels leads to PSCs apoptosis [ 70 , 71 , 72 , 73 , 74 ]. Moreover, studies demonstrated that targeting PSCs with antifibrotic or anti-inflammatory compounds in a form of siRNA or small molecules could prevent chronic pancreatitis progression [ 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 ].…”

Section: Discussionmentioning

confidence: 99%

5-FU-miR-15a Inhibits Activation of Pancreatic Stellate Cells by Reducing YAP1 and BCL-2 Levels In Vitro

Almanzar

Shah

LaComb

et al. 2023

IJMS

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Chronic pancreatitis is characterized by chronic inflammation and fibrosis, processes heightened by activated pancreatic stellate cells (PSCs). Recent publications have demonstrated that miR-15a, which targets YAP1 and BCL-2, is significantly downregulated in patients with chronic pancreatitis compared to healthy controls. We have utilized a miRNA modification strategy to enhance the therapeutic efficacy of miR-15a by replacing uracil with 5-fluorouracil (5-FU). We demonstrated increased levels of YAP1 and BCL-2 (both targets of miR-15a) in pancreatic tissues obtained from Ptf1aCreERTM and Ptf1aCreERTM;LSL-KrasG12D mice after chronic pancreatitis induction as compared to controls. In vitro studies showed that delivery of 5-FU-miR-15a significantly decreased viability, proliferation, and migration of PSCs over six days compared to 5-FU, TGFβ1, control miR, and miR-15a. In addition, treatment of PSCs with 5-FU-miR-15a in the context of TGFβ1 treatment exerted a more substantial effect than TGFβ1 alone or when combined with other miRs. Conditioned medium obtained from PSC cells treated with 5-FU-miR-15a significantly inhibits the invasion of pancreatic cancer cells compared to controls. Importantly, we demonstrated that treatment with 5-FU-miR-15a reduced the levels of YAP1 and BCL-2 observed in PSCs. Our results strongly suggest that ectopic delivery of miR mimetics is a promising therapeutic approach for pancreatic fibrosis and that 5-FU-miR-15a shows specific promise.

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Section: Discussionmentioning

confidence: 99%

5-FU-miR-15a Inhibits Activation of Pancreatic Stellate Cells by Reducing YAP1 and BCL-2 Levels In Vitro

Almanzar

Shah

LaComb

et al. 2023

IJMS

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“… 65 Second, transgenic mice expressing LIF from the insulin promoter displayed considerable interstitial fibrosis throughout the pancreas. 66 , 67 However, in the case of TIF, the results are still controversial. Matsumto et al.…”

Section: Discussionmentioning

confidence: 99%

Leukemia inhibitory factor is a therapeutic target for renal interstitial fibrosis

Xu¹,

Yang²,

Chen³

et al. 2022

eBioMedicine

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“…SNHG11 regulates leukemia inhibitory factor (LIF) expression by sequestering miR-34b. Considering the promotive role of miR-34b in PSC proliferation, migration, and matrix accumulation induced by TGF-β1, silencing SNHG11 through the miR-34b/LIF axis, shows promise for treating CP [144]. Long non-coding RNAs (LncRNAs) have also been recognized as key regulators of fibrosis-related diseases.…”

Section: Reg1-3mentioning

confidence: 99%

Activation and Regulation of Pancreatic Stellate Cells in Chronic Pancreatic Fibrosis: A Potential Therapeutic Approach for Chronic Pancreatitis

Kong,

Pan,

2024

Biomedicines

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In the complex progression of fibrosis in chronic pancreatitis, pancreatic stellate cells (PSCs) emerge as central figures. These cells, initially in a dormant state characterized by the storage of vitamin A lipid droplets within the chronic pancreatitis microenvironment, undergo a profound transformation into an activated state, typified by the secretion of an abundant extracellular matrix, including α-smooth muscle actin (α-SMA). This review delves into the myriad factors that trigger PSC activation within the context of chronic pancreatitis. These factors encompass alcohol, cigarette smoke, hyperglycemia, mechanical stress, acinar cell injury, and inflammatory cells, with a focus on elucidating their underlying mechanisms. Additionally, we explore the regulatory factors that play significant roles during PSC activation, such as TGF-β, CTGF, IL-10, PDGF, among others. The investigation into these regulatory factors and pathways involved in PSC activation holds promise in identifying potential therapeutic targets for ameliorating fibrosis in chronic pancreatitis. We provide a summary of recent research findings pertaining to the modulation of PSC activation, covering essential genes and innovative regulatory mediators designed to counteract PSC activation. We anticipate that this research will stimulate further insights into PSC activation and the mechanisms of pancreatic fibrosis, ultimately leading to the discovery of groundbreaking therapies targeting cellular and molecular responses within these processes.

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

Cited by 13 publications

References 35 publications

5-FU-miR-15a Inhibits Activation of Pancreatic Stellate Cells by Reducing YAP1 and BCL-2 Levels In Vitro

5-FU-miR-15a Inhibits Activation of Pancreatic Stellate Cells by Reducing YAP1 and BCL-2 Levels In Vitro

Leukemia inhibitory factor is a therapeutic target for renal interstitial fibrosis

Activation and Regulation of Pancreatic Stellate Cells in Chronic Pancreatic Fibrosis: A Potential Therapeutic Approach for Chronic Pancreatitis

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