Submandibular gland autotransplantation is effective for treating severe dry eye 
syndrome. However, more than 40% of patients show epiphora within 3-6 months 
after treatment. The mechanism underlying the hypersecretion in epiphora remains 
to be elucidated for developing novel interventions. Since salivary gland 
secretion is dependent on a variety of proteins, we analyzed the changes in 
protein expression in transplanted glands of epiphora patients with 2-D gel 
electrophoresis and electrospray ionization quadrupole/time-of-flight mass 
spectrometry and evaluated their possible roles in epiphora. There were 23 
proteins that showed altered expression in the glands of epiphora patients, 15 
being up-expressed and 8 being down-expressed. The expression of secretory 
proteins was decreased in these glands, including alpha-amylase, cystatin S, SA, 
and SN. In contrast, cytoskeletal proteins were all up-regulated, including 
actin and vimentin. Immunofluorescence revealed that the intensity ratio of 
F-actin in apical and lateral cytoplasm to total F-actin in acini was decreased 
in the glands of epiphora patients. Carbachol stimulation induced a similar 
redistribution of F-actin in the control glands. Phosphorylation of 
extracellular signal-regulated kinase 1/2 (ERK1/2) was increased in both 
carbachol-stimulated and epiphora glands. Preincubation of submandibular glands 
with ERK1/2 inhibitors PD98059 or U0126 inhibited carbachol-induced F-actin 
redistribution. These results indicated that differentially expressed proteins 
participated in the hypersecretion of transplanted submandibular glands and the 
redistribution of F-actin might be involved in this hypersecretion in an 
ERK1/2-dependent manner.