Molecular Cloning of Canine Protease-Activated Receptor-2 and its Expression in Normal Dog Tissues and Atopic Skin Lesions

Abstract

ABSTRACT. Protease-activated receptor-2 (PAR-2) belongs to a new G protein-coupled receptor subfamily and is activated by serine proteases. PAR-2 has been demonstrated to play an important role in inflammation and immune response in allergic diseases. In this study, we cloned canine PAR-2 cDNA from the canine kidney by RT-PCR. The canine PAR-2 clone contained a full-length open reading frame encoding 397 amino acids that had 84% and 80% homology with human and mouse homologues, respectively. Canine PAR-2 mRNA was detected in the heart, lung, liver, pancreas, stomach, small intestine, colon, kidney, adrenal gland, spleen, thyroid gland, thymus, skeletal muscle, lymph node, fat and skin of three healthy dogs. The expression pattern of PAR-2 mRNA in canine tissues was similar to that in humans. The expression level of PAR-2 mRNA in skin was not different between the atopic dermatitis (AD) and healthy dogs, suggesting that the level of PAR-2 mRNA transcription may not be associated with development of canine AD. The canine PAR-2 cDNA clone obtained in this study will be useful for further investigation of the immunopathogenesis of canine allergic diseases.

First report in a dog model of atopic dermatitis: expression patterns of protease‐activated receptor‐2 and thymic stromal lymphopoietin

“…The proteases from allergens are associated with various homeostatic responses in skin disease, such as inflammation, immune responses, host defense, chemotaxis, cytokine expression, vascular function, tissue repair and apoptosis . Serine proteases, such as trypsin or mast cell tryptase, can activate PAR‐2 signals . The present AD model, which was developed by HDM sensitization, could present some unique changes of the homeostatic responses.…”

“…In the present study, however, the intensity of PAR‐2 and TSLP in immunofluorescence was not significantly increased in atopic dogs compared with normal animals. Another study also reported that the mRNA level of PAR‐2 was not significantly different between atopic dogs (lesional skin) and normal animals; it concluded that the level of PAR‐2 mRNA transcription may not be associated with development of canine AD …”

A review of the roles of keratinocyte‐derived cytokines and chemokines in the pathogenesis of atopic dermatitis in humans and dogs

“…PARs belong to a subfamily of G protein‐coupled, 7‐transmembrane domain receptors, activated by specific proteolytic cleavage of their extracellular amino termini by proteases . Among PAR‐1 to ‐5, PAR‐2 has been shown to be expressed in the keratinocytes of humans, mice and dogs . Recent studies in humans and dogs have indicated that activation of TLRs and PAR‐2 in keratinocytes induces the production of cytokines and chemokines necessary for initiating and maintaining allergic inflammation.…”

“…36,37 Among PAR-1 to -5, PAR-2 has been shown to be expressed in the keratinocytes of humans, 38 mice 39 and dogs. 40,41 Recent studies in humans and dogs have indicated that activation of TLRs and PAR-2 in keratinocytes induces the production of cytokines and chemokines necessary for initiating and maintaining allergic inflammation.…”

Intestinal Protease-Activated Receptor-2 and Fecal Serine Protease Activity are Increased in Canine Inflammatory Bowel Disease and May Contribute to Intestinal Cytokine Expression

“…These findings suggest that the interactions between PAR-2 and luminal serine proteases may be associated with the pathogenesis of IBD. As in humans and rodents, PAR-2 is prominently expressed in the small intestine and colon in dogs [27], which indicates that PAR-2 may also play a role in gut inflammation in this species. However, little is known about the pathophysiological roles of PAR-2 and luminal serine proteases in canine IBD.…”