Table 1.

Roles of TRP channels in various skin diseases

Disease	Potential involvement of TRP channels	Putative therapeutic approaches and supporting evidence
‘Barrier-diseases’	TRPV1 Activation decreased proliferation and induced apoptosis of keratinocytes (Bodó et al., 2005; Tóth et al., 2011). Activation inhibited skin barrier recovery (Denda et al., 2007). Activation induced release of pro-inflammatory cytokines from keratinocytes (Southall et al., 2003; Bodó et al., 2005).	TRPV1 Antagonism or desensitization might be beneficial. Orally applied TRPV1 antagonist (PAC-14028) accelerated barrier recovery (Yun et al., 2011).
	TRPV4 Activation induced barrier recovery and promoted the tight-junction barrier between keratinocytes (Denda et al., 2007; Kida et al., 2012; Akazawa et al., 2013). Genetic deletion associated with leaky cell-cell junctions (Sokabe et al., 2010; Sokabe and Tominaga, 2010).	TRPV4 Activation might be beneficial.
	TRPV6 Indispensible for normal epidermal barrier formation and Ca2+ homeostasis of keratinocytes (Bouillon et al., 2006; Bianco et al., 2007; Lehen'kyi et al., 2007).	TRPV6 Activation might be beneficial. Avène Thermal Spring water increased TRPV6 channel expression and initiated a TRPV6-mediated Ca2+ entry which, in turn, resulted in differentiation (Lehen'kyi et al., 2011).
	TRPA1 Activation and inhibition accelerated and delayed barrier recovery respectively (Denda et al., 2010b).	TRPA1 Activation might be beneficial.
	TRPM8 Activation (WS12) potentiated the barrier recovery (Denda et al., 2010a).	TRPM8 Activation might be beneficial.
	TRPC1/4/6 Promoted differentiation of keratinocytes (Cai et al., 2006; Beck et al., 2008; Müller et al., 2008).	TRPC1/4/6 Activation might be beneficial.
Skin inflammation (e.g. atopic and contact dermatitis)	TRPV1 Activation induced release of pro-inflammatory cytokines from keratinocytes (Southall et al., 2003; Bodó et al., 2005).	TRPV1 Antagonism might be beneficial.
	TRPV3 Gain-of-function mutation resulted in AD-like phenotype in mice (Asakawa et al., 2006; Xiao et al., 2008; Yoshioka et al., 2009).	Antagonism or desensitization might be beneficial.
	TRPA1 It was found to be involved in mediating inflammation induced by various contact irritants/allergens (Liu et al., 2013).	TRPA1 Antagonism might be beneficial.
Hair growth disorders	TRPV1 Activation inhibited hair growth (Bodó et al., 2005).	TRPV1 Antagonism or desensitization might be beneficial in alopecia. Activation might be beneficial in hirsutism.
	TRPV3 Activation inhibited hair growth in vitro (Borbíró et al., 2011). Gain-of-function mutation resulted in hairless phenotype in mice (Asakawa et al., 2006; Imura et al., 2007).	TRPV3 Antagonism or desensitization might be beneficial in alopecia. Activation might be beneficial in hirsutism.
Prurigo nodularis	TRPV1 Elevated expression was detected in hyperkeratotic lesions of prurigo nodularis patients (Ständer et al., 2004).	TRPV1 Activation might be beneficial. Chronic topical capsaicin treatment ameliorated the symptoms (Ständer et al., 2001).
Psoriasis	TRPC1/4/5/6/7 Decreased expression was found (Leuner et al., 2011).	Activation or up-regulation might be beneficial.
Rosacea	TRPV1-4 Dysregulation of expression was observed (Sulk et al., 2012).
Acne vulgaris	TRPV1 Activation inhibited lipid production and suppressed IL-1β synthesis of sebocytes (Tóth et al., 2009a).	TRPV1 Activation might be beneficial.
Non-melanoma skin cancers	TRPC1/4 Lack of epidermal expression correlating with tumour cells' proliferation in BCC was reported (Beck et al., 2008).	TRPC1/4 Potential prognostic markers.
	TRPC6 Activation augmented cellular differentiation in actinic keratosis (in situ SCC) (Woelfle et al., 2010).	TRPC6 Activation might be beneficial.
Malignant melanoma	TRPM1 Expression correlated inversely with the metastatic potential of skin melanomas (Deeds et al., 2000; Duncan et al., 2001; Miller et al 2004; Zhiqi et al., 2004). miRNA211 coded in an intron of TRPM1 was shown to be responsible for the tumour-promoting effect of TRPM1 (Levy et al., 2010; Mazar et al., 2010; Boyle et al., 2011; Guo et al., 2012).	TRPM1 Down-regulation might be a prognostic marker for metastasis (Deeds et al., 2000; Duncan et al., 2001; Miller et al., 2004; Zhiqi et al., 2004).
	TRPM2 Augmented susceptibility to apoptosis (Orfanelli et al., 2008).	TRPM2 Activation might be beneficial.
	TRPM8 Expression was increased (Tsavaler et al., 2001). Activation induced Ca2+-dependent cell death (Slominski, 2008; Yamamura et al., 2008).	TRPM8 Potential prognostic marker. Activation might be beneficial.
Skin ageing and UV-induced diseases	TRPV1 It is involved in mediating the effect of UV exposure to induce inflammation and to up-regulate MMP-1 (Li et al., 2007; Lee et al., 2008b; 2009b; 2009b,2011). Increased expression was found in aged skin (Lee et al., 2009a).	TRPV1 Antagonisms might be beneficial. Antagonism inhibited UV-induced skin thickening, MMP and pro-inflammatory cytokine expression (Lee et al., 2011).
DA	TRPC1 It was found to be overexpressed and can contribute to pathomechanism via regulating Ca2+ influx (Barfield et al., 2002; Pani et al., 2006).	TRPC1 Antagonisms might be beneficial.
OS	TRPV3 Gain-of-function mutations were found to play a causal role in the disease (Lai-Cheong et al., 2012; Lin et al., 2012).	TRPV3 Antagonisms or targeted gene therapy might be beneficial.