Soluble ADAM33 determines mechanical behaviors of airway smooth muscle cells

Introduction A disintegrin and metalloproteinase 33（ADAM33）has been identified as a susceptibility gene for asthma[1],In particular,ADAM33 mRNA is highly expressed in airway smooth muscle cells（ASMCs）and the level of soluble ADAM33（sADAM33）is known to inversely correlate with lung function such as bronchial hyperresponsiveness（BHR）[2]that is ultimately determined by the mechanical behaviors of ASMCs.However,few have studied how sADAM33would affect ASMC mechanics.Here,we manipulated the expression of SADAM33 in

The effect of inhibitor peptide for ADAM8 in attenuating ovalbumin-induced murine asthma

Targeted peptides have been identified as showing great promise for treatment of various diseases including asthma.Asthma is considered of difficuIt-to-treat due to its unclear etiology,thus usually requiring life-long treatment.Current strategies for asthma therapy are hampered with undesirable side effects,poor targeting and failure in modulating airway hyperresponsiveness,leading to pressing need of developing more targeted and effective therapeutic sites for asthma.Recently,a disintegrin and metalloproteinase 8(ADAM8)have been shown to over-

Spheroids of Endothelial Cells and Vascular Smooth Muscle Cells Promote Cell Migration in Hyaluronic Acid and Fibrinogen Composite Hydrogels

Cell migration plays a pivotal role in many pathological and physiological processes.So far,most of the studies have been focused on 2-dimensional cell adhesion and migration.Herein,the migration behaviors of cell spheroids in 3D hydrogels obtained by polymerization of methacrylated hyaluronic acid(HA-MA)and fibrinogen(Fg)with different ratios were studied.The Fg could be released to the medium gradually along with time prolongation,achieving the dynamic change of hydrogel structures and properties.Three types of cell spheroids,i.e.,endothelial cell(EC),smooth muscle cell(SMC),and EC-SMC spheroids,were prepared with 10,000 cells in each,whose diameters were about 343,108,and 224μm,respectively.The composite hydrogels with an intermediate ratio of Fg allowed the fastest 3D migration of cell spheroids.The ECs-SMCs migrated longest up to 3200μm at day 14,whereas the SMC spheroids migrated slowest with a distance of only~400μm at the same period of time.The addition of free RGD or anti-CD44 could significantly reduce the migration distance,revealing that the cell-substrate interactions take the major roles and the migration is mesenchymal dependent.Moreover,addition of anti-N-cadherin and MMP inhibitors also slowed down the migration rate,demonstrating that the degradation of hydrogels and cell-cell interactions are also largely involved in the cell migration.RT-PCR measurement showed that expression of genes related to cell adhesion and antiapoptosis,and angiogenesis was all upregulated in the EC-SMC spheroids than single EC or SMC spheroids,suggesting that the use of composite cell spheroids is more promising to promote cell-substrate interactions and maintenance of cell functions.