The Oligo Fucoidan Inhibits Platelet-Derived Growth Factor-Stimulated Proliferation of Airway Smooth Muscle Cells

Abstract

In the pathogenesis of asthma, the proliferation of airway smooth muscle cells (ASMCs) is a key factor in airway remodeling and causes airway narrowing. In addition, ASMCs are also the effector cells of airway inflammation. Fucoidan extracted from marine brown algae polysaccharides has antiviral, antioxidant, antimicrobial, anticlotting, and anticancer properties; however, its effectiveness for asthma has not been elucidated thus far. Platelet-derived growth factor (PDGF)-treated primary ASMCs were cultured with or without oligo-fucoidan (100, 500, or 1000 µg/mL) to evaluate its effects on cell proliferation, cell cycle, apoptosis, and Akt, ERK1/2 signaling pathway. We found that PDGF (40 ng/mL) increased the proliferation of ASMCs by 2.5-fold after 48 h (p < 0.05). Oligo-fucoidan reduced the proliferation of PDGF-stimulated ASMCs by 75%–99% after 48 h (p < 0.05) and induced G1/G0 cell cycle arrest, but did not induce apoptosis. Further, oligo-fucoidan supplementation reduced PDGF-stimulated extracellular signal-regulated kinase (ERK1/2), Akt, and nuclear factor (NF)-κB phosphorylation. Taken together, oligo-fucoidan supplementation might reduce proliferation of PDGF-treated ASMCs through the suppression of ERK1/2 and Akt phosphorylation and NF-κB activation. The results provide basis for future animal experiments and human trials.

Decreased S100A9 Expression Promoted Rat Airway Smooth Muscle Cell Proliferation by Stimulating ROS Generation and Inhibiting p38 MAPK

“…ASMCs proliferation plays a key role in asthma airway remodeling and involves various signal transduction pathways and mediators, such as reactive oxygen species (ROS) and p38 mitogen-activated protein kinase (MAPK) [5, 6]. ROS can act as second messengers to regulate different signaling pathways, and they are important mediators of cellular proliferation [7].…”

Oligo‑fucoidan improved unbalance the Th1/Th2 and Treg/Th17 ratios in asthmatic patients: An ex vivo study

“…Recent studies indicate that fucoidan can improve allergic responses by regulating the immune response, including alterations in the Th1/Th2 balance, inhibiting the production of IgE, suppressing the degranulation of mast cells, and inhibiting the proliferation of ASM (23). At present, little has been done to explore on the use of fucoidan in allergic diseases.…”

“…Treatment of atopic allergic reactions with various fucoidan extracts improves allergic responses and prevents or reduces the symptoms of allergic disease by regulating the immune response, including an alteration in the Th1/Th2 balance, an inhibition of IgE production, and a suppression of mast cells degranulation (21,22). In our previous study, we found that oligo-fucoidan might reduce the proliferation of airway smooth muscle (ASM) cells (23). However, the effects of oligo-fucoidan on T cells during allergic disease remains unclear.…”

Macrophage migration inhibitory factor (MIF) promotes rat airway muscle cell proliferation and migration mediated by ERK1/2 and FAK signaling

“…The pathogenesis of airway remodeling in asthma involves an increase of the ASM mass, potentially resulting from an increase of ASMC proliferation and a decrease of apoptosis. PDGFBB is a well‐known growth factor that stimulates the proliferation of ASMCs (Ito et al, ; Hirota et al, ; Yang et al, ). Interestingly, we observed that PDGFBB upregulated the expression of MIF, which has been reported to promote cell proliferation in several studies (Lacey et al, ; Guo et al, ; Xie and Xi, ).…”

“…However, little information is available in the literature regarding a potential role of MIF in ASMCs, especially the effect of MIF on cell proliferation, migration, and apoptosis. Since it is well documented that platelet‐derived growth factor‐BB (PDGFBB) promotes the proliferation of ASMCs (Ito et al, ; Chen et al, ; Hirota et al, ; Yang et al, ), we first tested whether PDGFBB stimulates the expression of MIF. Then, we investigated the effects of MIF on proliferation, migration, and activation of ERK and focal adhesion kinase (FAK) in ASMCs infected with recombinant adenovirus containing wild‐type MIF cDNA (Ad‐MIF) or a green fluorescent protein (GFP)‐expressing adenovirus vector (Ad‐GFP) as a control virus.…”