Prostatic acid phosphatase is the main acid phosphatase with 5'-ectonucleotidase activity in the male mouse saliva and regulates salivation.
We have previously shown that in addition to the well-known secreted isoform of prostatic acid phosphatase (sPAP), a transmembrane isoform exists (TMPAP) that interacts with snapin (a SNARE-associated protein) and regulates the endo-/exocytic pathways. We have also shown that PAP has 5'-ectonucleotidase and thiamine monophosphatase activity and elicits antinociceptive effects in mouse models of chronic inflammatory and neuropathic pain. Therefore, to determine the physiological role of PAP in a typical exocrine organ, we studied the submandibular salivary gland (SMG) of PAP(-/-) and wild-type C57BL/6J mice by microarray analyses, microRNA sequencing, activity tests, immunohistochemistry, and biochemical and physiological analyses of saliva. We show that PAP is the main acid phosphatase in the wild-type male mouse saliva, accounting for 50% of the total acid phosphatase activity, and that it is expressed only in the granular convoluted tubules of the SMGs, where it is the only 5'-ectonucleotidase. The lack of PAP in male PAP(-/-) mice was associated with a significant increase in the salivation volume under secretagogue stimulation, overexpression of genes related to cell proliferation (Mki67, Aurkb, Birc5) and immune response (Irf7, Cxcl9, Ccl3, Fpr2), and upregulation of miR-146a in SMGs. An increased and sustained acinar cell proliferation was detected without signs of glandular hyperplasia. Our results indicate that in PAP(-/-) mice, SMG homeostasis is maintained by an innate immune response. Additionally, we suggest that in male mice, PAP via its 5'-ectonucleotidase activity and production of adenosine can elicit analgesic effects when animals lick their wounds.
Department of Clinical Chemistry, University of Helsinki and Helsinki University Hospital Laboratory, Helsinki, Finland;
César L
CL
Araujo
Department of Clinical Chemistry, University of Helsinki and Helsinki University Hospital Laboratory, Helsinki, Finland;
Ileana B
IB
Quintero
Finnish Centre for Laboratory Animal Pathology, Faculty of Veterinary Science, University of Helsinki, Helsinki, Finland; and.
Anja
A
Kipar
Department of Clinical Chemistry, University of Helsinki and Helsinki University Hospital Laboratory, Helsinki, Finland;
Annakaisa M
AM
Herrala
Department of Clinical Chemistry, University of Helsinki and Helsinki University Hospital Laboratory, Helsinki, Finland;
Anitta E
AE
Pulkka
Research Programs Unit; Genome-scale Biology and Institute of Biomedicine, University of Helsinki, Helsinki, Finland;
Lilli
L
Saarinen
Research Programs Unit; Genome-scale Biology and Institute of Biomedicine, University of Helsinki, Helsinki, Finland;
Sampsa
S
Hautaniemi
Department of Clinical Chemistry, University of Helsinki and Helsinki University Hospital Laboratory, Helsinki, Finland; Veterinary Pathology, School of Veterinary Science and Department of Infection Biology, Institute of Infection and Global Health, University of Liverpool, Liverpool, United Kingdom pirkko.vihko@helsinki.fi.
Pirkko
P
Vihko
D000135:Acid Phosphatase / Q000032:analysis / Q000378:metabolism; D000818:Animals; D004789:Enzyme Activation / Q000502:physiology; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017027:Protein Tyrosine Phosphatases / Q000032:analysis / Q000378:metabolism*; D012463:Saliva / Q000737:chemistry / Q000201:enzymology*; D012472:Salivation / Q000502:physiology*
D000135:Acid Phosphatase; C428439:prostatic acid phosphatase; D017027:Protein Tyrosine Phosphatases
5′-ectonucleotidase activity; TMPase activity; acid phosphatase; submandibular salivary gland; transmembrane prostatic acid phosphatase