S100A11 mediates hypoxia-induced mitogenic factor (HIMF)-induced smooth muscle cell migration, vesicular exocytosis, and nuclear activation.
Hypoxia-induced mitogenic factor (HIMF) is a newly discovered protein that is up-regulated in murine models of pulmonary arterial hypertension and asthma. Our previous study shows that HIMF is a potent mitogenic, angiogenic, and vasoconstrictive chemokine associated with pulmonary arterial hypertension. Two-dimensional gel electrophoresis was used to investigate downstream molecules in HIMF-induced cell signaling, demonstrating that S100A11, an EF-hand calcium-binding protein, was exclusively altered and was decreased (2.7±0.2-fold, p<0.05) in pulmonary artery smooth muscle cells (SMCs) treated with HIMF for 5 min compared with untreated cells (n=4). Immunofluorescence showed that in control cells S100A11 is a cytosolic protein, which then aggregates and translocates both to the plasma membrane with subsequent exocytosis and to the nucleus upon HIMF stimulation. Annexin A2, a known S100A11 binding partner, also colocalized with S100A11 during HIMF-induced membrane trafficking. To investigate the intracellular function of S100A11, siRNA was used to knock down S100A11 expression in SMCs. The S100A11 knockdown significantly reduced HIMF-induced SMC migration but did not affect the SMC mitogenic action of HIMF. Our data show that S100A11 mediates HIMF-induced smooth muscle cell migration, vesicular exocytosis, and nuclear activation.
Department of Anesthesiology and Critical Care Medicine, School of Medicine, The Johns Hopkins University, Baltimore, MD 21205, USA.
Chunling
C
Fan
Zongming
Z
Fu
Qingning
Q
Su
Daniel J
DJ
Angelini
Jennifer
J
Van Eyk
Roger A
RA
Johns
D017306:Annexin A2 / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects*; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D005089:Exocytosis / Q000187:drug effects*; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism / Q000494:pharmacology*; D032389:Myocytes, Smooth Muscle / Q000166:cytology*; D021381:Protein Transport / Q000187:drug effects; D011651:Pulmonary Artery / Q000166:cytology; D009418:S100 Proteins / Q000378:metabolism*; D022142:Secretory Vesicles / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
D017306:Annexin A2; D036341:Intercellular Signaling Peptides and Proteins; D009418:S100 Proteins; C072337:S100A11 protein, human; D002118:Calcium