Interleukin-6 participates in human pancreatic stellate cell activation and collagen I production via TGF-β1/Smad pathway

Liver cirrhosis is currently the 11th most common cause of death which includes inflammatory, oxidative damage, and immune response. Harmaline has antioxidant and anti-inflammatory mechanisms which can defeat against hepatic cirrhosis pathways. The present work aimed to evaluate the ameliorating effect of harmaline against liver cirrhosis induced by thioacetamide in mice. The study was carried out on sixty male mice divided into three main groups. Control and harmaline groups (GIa and GIb), thioacetamide-group (GII) and harmaline co-treated and treated groups (GIIIa and GIIIb). By the end of the experiment, adiponectin concentrations were measured in serum and liver tissue. Gene expression of adiponectin, transforming growth factor beta-1 (TGF-β1), tissue inhibitor metalloprotease-1(TIMP-1) and peroxisome proliferator activated receptor-gamma (PPAR-γ) were assessed. Some oxidative stress biomarkers as malondialdehyde, reduced glutathione, catalase, superoxide dismutase and nitric oxide were determined. The results indicated that harmaline administration cause significant suppression of oxidative stress and inflammatory response.Inhibition of hepatic stellate cell activation and extracellular matrix deposition were also noticed with a significant decrease in the expression of the profibrotic markers(TGF-β1 and TIMP-1) which have direct effects on adiponectin activation. These results were confirmed by the histological studies in liver tissue. In Conclusion,Harmaline has excellent protective role against liver cirrhosis induced by thioacetamide in mice via its antioxidant and anti-inflammatory properties.It can be therapeutically used as a safe liver support by a dose of 10 mg/kg after furtherin vivo studies.

Download Full-text

Pancreatic Stellate Cell Activation by Ethanol and Acetaldehyde: Is it Mediated by the Mitogen-Activated Protein Kinase Signaling Pathway?

Pancreas ◽

10.1097/00006676-200308000-00008 ◽

2003 ◽

Vol 27 (2) ◽

pp. 150-160 ◽

Cited By ~ 62

Author(s):

J. A. McCarroll ◽

P. A. Phillips ◽

S. Park ◽

E. Doherty ◽

R. C. Pirola ◽

...

Keyword(s):

Protein Kinase ◽

Signaling Pathway ◽

Cell Activation ◽

Stellate Cell ◽

Mitogen Activated Protein Kinase ◽

Kinase Signaling ◽

Pancreatic Stellate Cell ◽

Mitogen Activated Protein ◽

Protein Kinase Signaling ◽

Kinase Signaling Pathway

Download Full-text

Pancreatic stellate cell‐potentiated insulin secretion from Min6 cells is independent of interleukin 6‐mediated pathway

Journal of Cellular Biochemistry ◽

10.1002/jcb.29329 ◽

2019 ◽

Vol 121 (1) ◽

pp. 840-855

Author(s):

Ratnakar R. Bynigeri ◽

Sasikala Mitnala ◽

Rupjyoti Talukdar ◽

Surya S. Singh ◽

Nageshwar R. Duvvuru

Keyword(s):

Insulin Secretion ◽

Interleukin 6 ◽

Stellate Cell ◽

Pancreatic Stellate Cell ◽

Min6 Cells

Download Full-text

Participation of miR-200a in TGF-β1-mediated hepatic stellate cell activation

Molecular and Cellular Biochemistry ◽

10.1007/s11010-013-1895-0 ◽

2013 ◽

Vol 388 (1-2) ◽

pp. 11-23 ◽

Cited By ~ 52

Author(s):

Xu Sun ◽

Yong He ◽

Tao-Tao Ma ◽

Cheng Huang ◽

Lei Zhang ◽

...

Keyword(s):

Hepatic Stellate Cell ◽

Cell Activation ◽

Stellate Cell ◽

Hepatic Stellate Cell Activation ◽

Tgf Β1

Download Full-text

Calycosin Inhibits Intestinal Fibrosis on CCD-18Co Cells via Modulating Transforming Growth Factor-β/Smad Signaling Pathway

Pharmacology ◽

10.1159/000500186 ◽

2019 ◽

Vol 104 (1-2) ◽

pp. 81-89 ◽

Cited By ~ 3

Author(s):

Jing Liu ◽

Tan Deng ◽

Yaxin Wang ◽

Mengmeng Zhang ◽

Guannan Zhu ◽

...

Keyword(s):

Growth Factor ◽

Signaling Pathway ◽

Transforming Growth Factor ◽

Smooth Muscle Actin ◽

Collagen I ◽

Smad Pathway ◽

Smad Signaling ◽

Intestinal Fibrosis ◽

Smad Signaling Pathway ◽

Tgf Β1

Background: Intestinal fibrosis is the major complication of Crohn’s disease (CD). There are no other good treatments for CD except surgery and remains a refractory disease. Calycosin (CA), the active component of astragalus membranaceus, has been reported the potential effect on lung fibrosis and renal fibrosis. In this study, we aim to explore the effect of CA on intestinal fibrosis in vitro and the possible signal pathway. Methods: The antifibrotic effect of CA is investigated in human intestinal fibroblasts (CCD-18Co) cells induced by transforming growth factor-β1 (TGF-β1). MTT method was used to screen the concentration of CA. Real-time polymerase chain reaction and western blot analysis were used to evaluate the expression of α-smooth muscle actin (α-SMA), collagen I, and TGF-β/Smad pathway. Results: The results showed that the concentration of CA was 12.5, 25, 50 μmol/L. CA could inhibit the expression of α-SMA and collagen I. In addition, CA regulated the expression of TGF-β/Smad signaling pathway. Conclusion: This study demonstrated that CA could inhibit the activation of CCD-18Co cells and reduce the expression of extracellular matrix. Our study highlighted that CA-inhibited TGF-β/Smad pathway through inhibiting the expression of p-Smad2, p-Smad3, Smad4, and TGF-β1 and raised the Smad7 expression. Therefore, CA might inhibit intestinal fibrosis by inhibiting the TGF-β/Smad pathway.

Download Full-text