Abstract
Post-burn pruritus is a common and distressing sequela of burn scars. Empirical antipruritic treatments usually fail to have a satisfactory outcome because of their limited selectivity and possible side effects. Therefore, novel drug targets need to be identified. Here, we aimed to investigate the possible role of protease-activated receptor 2 (PAR2) and transient receptor potential vanniloid 3 (TRPV3), along with the relation of TRPV3 to thymic stromal lymphopoietin (TSLP). Specimens from normal (unscarred) or burn-scarred (with or without pruritus) tissue were obtained from burn patients for this study. In each sample, the keratinocytes were isolated and cultured, and the intracellular Ca2+ level at the time of stimulation of each factor was quantified and the interaction was screened. PAR2 function was reduced by antagonism of TRPV3. Inhibiting protein kinase A (PKA) and protein kinase C (PKC) reduced TRPV3 function. TSLP mRNA and protein, and TSLPR protein expressions, increased in scars with post-burn pruritus, compared to scars without it or to normal tissues. In addition, TRPV1 or TRPV3 activation induced increased TSLP expression. Conclusively, TRPV3 may contribute to pruritus in burn scars through TSLP, and can be considered a potential therapeutic target for post-burn pruritus.
Highlights
Transient receptor potential (TRP) channels are an ion channel group located in the plasma membrane of numerous types of cells
In this study we demonstrated the relationships of protease-activated receptor 2 (PAR2), transient receptor potential vanniloid 3 (TRPV3) and thymic stromal lymphopoietin (TSLP) in keratinocytes from scarsIwn tithhisosrtuwdityhwouetdpermurointustsr.ated the relationships of PAR2, TRPV3 and TSLP in keratinocytes from scarsPwAiRths oarrewwithidoeultyperuxprirteusss.ed G-protein coupled receptors, differentially activated by various physiPoAloRgsicaalrefacwtoidrselsyucehxpasretshsreodmGbi-np(rPoAteRin1, cPoAuRp3leadndrePcAepRt4o)r,sm, adsitffceerlel-ndteiarlilvyedactrtiyvpattaesdeiaonuds ptrhyypssiionlo(PgAicRal2faanctdorPsAsRu4c)h, washtichhrommebdiinat(ePAvaRr1io,uPsAsRig3naanlsd[1P8A,1R94].),PmARas2t ccaenll-bdeearicvtievdatterydpbtyasper(oPteAaRse2s) afrnodmtcriyrpcusilnati(oPnA, Rin2flaanmdmPaAtoRry4)c,ewllsh,incheumroendsiaatnedvkaerriaotuinsosciygtneasl;san[1d8,c1o9n]t.rPolAsRin2flcaamnmbaetiaocnt,ivpaatiendanbdy pneroutreoansaelsexfcriotambilitcyir[c2u0l–a2ti2o]n
In contrast with TRP vanilloid 1 (TRPV1), TRPV4 and TRP ankyrin 1 (TRPA1), which are reportedly sensitized by PAR2 activation in keratinocytes and neurons, there has been no report on the relationship of TRPV3 with PAR2 [7,8,9]
Summary
Transient receptor potential (TRP) channels are an ion channel group located in the plasma membrane of numerous types of cells. In a few of the early studies, the absence of TRPV3 in the TRP channels of skin cells was reported, but this finding was later reversed [2,3]. Besides skin and neuronal cells, TRPV3 is expressed in the nasal and oral cavities [4]. We evaluated the clinical and histopathological characteristics of patients with post-burn pruritus and discovered increased expression of TRPV3, TRPV4 and TRPA1 [5]. TRPV3, in particular, is predominantly expressed in the epidermis of the tissue of pruritic burn scars.
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