ADAM33 protein expression and the mechanics of airway smooth muscle cells are highly correlated in ovalbumin-sensitized rats.
A disintegrin and metalloproteinase 33 (ADAM33) has been identified as an asthma susceptibility gene; however, the role of ADAM33 in the pathogenesis and progression of asthma remains to be elucidated. As ADAM33 is predominantly expressed in airway smooth muscle cells (ASMCs), it is feasible to investigate whether ADAM33 protein expression is correlated with ASMC mechanics that are ultimately responsible for airway hyperresponsiveness in asthma. To determine this, Sprague Dawley rats were sensitized with ovalbumin (OVA) for up to 12 weeks to simulate asthma symptoms. Subsequently, ASMCs were isolated from the rats and cultured in vitro. The protein expression of ADAM33 and cytoskeletal proteins (including F‑actin and vinculin), cell stiffness and contractility, as well as traction force were measured. The results demonstrated that compared with the non‑sensitized rats, the protein expression of ADAM33 in ASMCs from the OVA‑sensitized rats increased in a time‑dependent manner, reaching a maximum level at 4 weeks of sensitization and gradually subsiding as OVA sensitization continued (P<0.001). The cell stiffness, traction force and expression of vinculin and F‑actin changed similarly, resulting in a positive correlation with ADAM33 protein expression (Pearson's correlation coefficient, 0.864, 0.716, 0.774 and 0.662, respectively; P=0.1‑0.3). The in vivo results of OVA‑induced ADAM33 protein expression and its association with the mechanics of ASMCs suggested that ADAM33 is a mediator of ASMC dysfunction in asthma, and may provide a rationale for the therapeutic targeting of ADAM33 in the treatment of asthma.
Key Laboratory of Biorheological Science and Technology, Ministry of Education, Bioengineering College, Chongqing University, Chongqing 400044, P.R. China.
Feng
F
Lin
Aijing
A
Song
Jiamin
J
Wu
Xuemei
X
Jiang
Jiaoyue
J
Long
Jun
J
Chen
Yiyuan
Y
Duan
Yanling
Y
Shi
Linhong
L
Deng
D051722:ADAM Proteins / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001249:Asthma / Q000201:enzymology* / Q000473:pathology; D001696:Biomechanical Phenomena; D002448:Cell Adhesion; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000378:metabolism; D004790:Enzyme Induction; D015870:Gene Expression; D008297:Male; D009119:Muscle Contraction; D032389:Myocytes, Smooth Muscle / Q000201:enzymology* / Q000276:immunology / Q000502:physiology; D010047:Ovalbumin / Q000276:immunology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012137:Respiratory System / Q000473:pathology; D016596:Vinculin / Q000378:metabolism
C488956:Vcl protein, rat; D016596:Vinculin; D010047:Ovalbumin; D051722:ADAM Proteins; C499183:Adam33 protein, mouse