Abstract
Adiponectin functions as a promoter of saliva secretion in rat submandibular gland via activation of adenosine monophosphate-activated protein kinase (AMPK) and increased paracellular permeability. Ca2+ mobilization is the primary signal for fluid secretion in salivary acinar cells. However, whether intracellular Ca2+ mobilization is involved in adiponectin-induced salivary secretion is unknown. Here, we found that full-length adiponectin (fAd) increased intracellular Ca2+ and saliva secretion in submandibular glands. Pre-perfusion with ethylene glycol-bis (2-aminoethylether)-N,N,N′,N′-tetraacetic acid (EGTA) combined with thapsigargin (TG), an endoplasmic reticulum Ca2+-ATPase inhibitor, abolished fAd-induced salivary secretion, AMPK phosphorylation, and enlarged tight junction (TJ) width. Furthermore, in cultured SMG-C6 cells, co-pretreatment with EGTA and TG suppressed fAd-decreased transepithelial electrical resistance and increased 4-kDa FITC-dextran flux responses. Moreover, fAd increased phosphorylation of calcium/calmodulin-dependent protein kinase (CaMKKβ), a major kinase that is activated by elevated levels of intracellular Ca2+, but not liver kinase B1 phosphorylation. Pre-perfusion of the isolated gland with STO-609, an inhibitor of CaMKKβ, abolished fAd-induced salivary secretion, AMPK activation, and enlarged TJ width. CaMKKβ shRNA suppressed, whereas CaMKKβ re-expression rescued fAd-increased paracellular permeability. Taken together, these results indicate that adiponectin induced Ca2+ modulation in rat submandibular gland acinar cells. Ca2+-CaMKKβ pathway is required for adiponectin-induced secretion through mediating AMPK activation and increase in paracellular permeability in rat submandibular glands.
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This study was supported by the National Natural Science Foundation of China 81771088 (CD), 81200799 (CD) and Tai Sheng Dental Medicine Development Fund (GYY).
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CD performed the major experiments and wrote the manuscript. ZHD and SLL participated in data interpretation and manuscript improvement. LLW and GYY designed the study, analyzed the data, and wrote the manuscript. All authors read and approved the final manuscript.
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Ding, C., Du, ZH., Li, SL. et al. Ca2+-CaMKKβ pathway is required for adiponectin-induced secretion in rat submandibular gland. J Mol Hist 49, 99–110 (2018). https://doi.org/10.1007/s10735-017-9750-3
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DOI: https://doi.org/10.1007/s10735-017-9750-3