List of Publications (2011-Current)
2026
Lee, Wook-Joo; Shim, Won-Sik
TRPV4 Activation Promotes Hair Growth via TSLP Signaling in the Skin Journal Article
In: Biomol Ther (Seoul), vol. 34, no. 4, pp. 942–952, 2026, ISSN: 2005-4483.
Abstract | Links | BibTeX | Tags: Hair, TRPV4, TSLP
@article{Lee2026,
title = {TRPV4 Activation Promotes Hair Growth via TSLP Signaling in the Skin},
author = {Wook-Joo Lee and Won-Sik Shim},
doi = {10.4062/biomolther.2026.080},
issn = {2005-4483},
year = {2026},
date = {2026-07-01},
urldate = {2026-07-01},
journal = {Biomol Ther (Seoul)},
volume = {34},
number = {4},
pages = {942--952},
publisher = {The Korean Society of Applied Pharmacology},
abstract = {Hair follicle cycling is regulated by complex signaling networks that coordinate stem cell activation and quiescence. Although transient receptor potential vanilloid 4 (TRPV4) is expressed in the skin and implicated in cutaneous physiology, its role in hair growth remains unclear. Here, we investigated the contribution of TRPV4 activation to hair growth and its relationship with thymic stromal lymphopoietin (TSLP). Pharmacological activation of TRPV4 using GSK1016790A significantly promoted hair regrowth and elongation in mice, whereas TRPV4 inhibition attenuated these effects. Consistently, Trpv4⁻/⁻ mice exhibited spontaneous hair loss, supporting a role for TRPV4 in maintaining hair homeostasis. TRPV4 activation increased TSLP production in the skin, and exogenous TSLP recapitulated the pro-growth effects of TRPV4 activation. These effects were suppressed by pharmacological blockade of the TSLP receptor, indicating TSLP-dependent signaling. Notably, TSLP restored hair growth in Trpv4⁻/⁻ mice, whereas TRPV4 activation did not, supporting the notion that TSLP acts downstream of TRPV4. In contrast, activation of TRPV3, another TRP channel abundantly expressed in the skin, did not significantly affect hair growth, highlighting the specific role of TRPV4 in this process. Overall, these findings identify a TRPV4-TSLP signaling axis that promotes hair growth and regulates hair follicle function, suggesting a potential therapeutic target for hair loss disorders.},
keywords = {Hair, TRPV4, TSLP},
pubstate = {published},
tppubtype = {article}
}
Hair follicle cycling is regulated by complex signaling networks that coordinate stem cell activation and quiescence. Although transient receptor potential vanilloid 4 (TRPV4) is expressed in the skin and implicated in cutaneous physiology, its role in hair growth remains unclear. Here, we investigated the contribution of TRPV4 activation to hair growth and its relationship with thymic stromal lymphopoietin (TSLP). Pharmacological activation of TRPV4 using GSK1016790A significantly promoted hair regrowth and elongation in mice, whereas TRPV4 inhibition attenuated these effects. Consistently, Trpv4⁻/⁻ mice exhibited spontaneous hair loss, supporting a role for TRPV4 in maintaining hair homeostasis. TRPV4 activation increased TSLP production in the skin, and exogenous TSLP recapitulated the pro-growth effects of TRPV4 activation. These effects were suppressed by pharmacological blockade of the TSLP receptor, indicating TSLP-dependent signaling. Notably, TSLP restored hair growth in Trpv4⁻/⁻ mice, whereas TRPV4 activation did not, supporting the notion that TSLP acts downstream of TRPV4. In contrast, activation of TRPV3, another TRP channel abundantly expressed in the skin, did not significantly affect hair growth, highlighting the specific role of TRPV4 in this process. Overall, these findings identify a TRPV4-TSLP signaling axis that promotes hair growth and regulates hair follicle function, suggesting a potential therapeutic target for hair loss disorders.
Kim, Yejoon; Choi, Junhyeok; Kim, Minjun; Rawal, Diwas; Lee, Wook-Joo; Shim, Won-Sik
Vitexin alleviates atopic dermatitis–associated itch via TRPV4 inhibition in sensory neurons and MRGPRX2/MrgprB2 blockade in mast cells Journal Article
In: International Immunopharmacology, vol. 168, 2026, ISSN: 1567-5769.
Abstract | Links | BibTeX | Tags: Atopic dermatitis, Itch, Mast cell, MrgprB2, MRGPRX2, Sensory neurons, TRPV4
@article{Kim2026,
title = {Vitexin alleviates atopic dermatitis–associated itch via TRPV4 inhibition in sensory neurons and MRGPRX2/MrgprB2 blockade in mast cells},
author = {Yejoon Kim and Junhyeok Choi and Minjun Kim and Diwas Rawal and Wook-Joo Lee and Won-Sik Shim},
doi = {10.1016/j.intimp.2025.115757},
issn = {1567-5769},
year = {2026},
date = {2026-01-00},
urldate = {2026-01-00},
journal = {International Immunopharmacology},
volume = {168},
publisher = {Elsevier BV},
abstract = {Chronic itch is a debilitating symptom in atopic dermatitis (AD), often resistant to current antipruritic therapies. Here, we demonstrate that vitexin (VTX) exerts antipruritic effects through modulation of neuronal and mast cell pathways. Calcium imaging in TRPV4-transfected HEK293T cells and primary mouse dorsal root ganglion neurons demonstrated that VTX substantially inhibited TRPV4-dependent calcium influx, reducing both peak responses and the proportion of agonist-responsive neurons. Parallel assays in HEK293T cells expressing human MRGPRX2 and murine MrgprB2 revealed dose-dependent suppression of compound 48/80-induced calcium signaling. Mast-cell degranulation assays indicated that VTX markedly decreased β-hexosaminidase release from primary mouse peritoneal mast cells and HMC1.2 cells upon compound 48/80 stimulation. In silico molecular docking analysis showed that VTX occupied overlapping binding regions with known agonists in TRPV4 and MRGPRX2/MrgprB2, suggesting direct receptor interactions. In an MC903-induced murine model of AD, VTX reduced scratching behavior, mast cell activation, and transcriptional upregulation of Trpv4 and MrgprB2. Notably, antipruritic effects were enhanced in Trpv4-deficient mice, indicating the contribution of MRGPRX2/MrgprB2 suppression. These findings identify VTX as a promising antipruritic candidate for AD-associated pruritus, and mechanistic insights provide a rationale for further exploration of VTX in advanced AD models and eventual translation to clinical therapies.},
keywords = {Atopic dermatitis, Itch, Mast cell, MrgprB2, MRGPRX2, Sensory neurons, TRPV4},
pubstate = {published},
tppubtype = {article}
}
Chronic itch is a debilitating symptom in atopic dermatitis (AD), often resistant to current antipruritic therapies. Here, we demonstrate that vitexin (VTX) exerts antipruritic effects through modulation of neuronal and mast cell pathways. Calcium imaging in TRPV4-transfected HEK293T cells and primary mouse dorsal root ganglion neurons demonstrated that VTX substantially inhibited TRPV4-dependent calcium influx, reducing both peak responses and the proportion of agonist-responsive neurons. Parallel assays in HEK293T cells expressing human MRGPRX2 and murine MrgprB2 revealed dose-dependent suppression of compound 48/80-induced calcium signaling. Mast-cell degranulation assays indicated that VTX markedly decreased β-hexosaminidase release from primary mouse peritoneal mast cells and HMC1.2 cells upon compound 48/80 stimulation. In silico molecular docking analysis showed that VTX occupied overlapping binding regions with known agonists in TRPV4 and MRGPRX2/MrgprB2, suggesting direct receptor interactions. In an MC903-induced murine model of AD, VTX reduced scratching behavior, mast cell activation, and transcriptional upregulation of Trpv4 and MrgprB2. Notably, antipruritic effects were enhanced in Trpv4-deficient mice, indicating the contribution of MRGPRX2/MrgprB2 suppression. These findings identify VTX as a promising antipruritic candidate for AD-associated pruritus, and mechanistic insights provide a rationale for further exploration of VTX in advanced AD models and eventual translation to clinical therapies.
2022
Sanjel, Babina; Kim, Bo‐Hyun; Song, Myung‐Hyun; Carstens, Earl; Shim, Won‐Sik
Glucosylsphingosine evokes pruritus via activation of 5‐HT2A receptor and TRPV4 in sensory neurons Journal Article
In: British J Pharmacology, vol. 179, no. 10, pp. 2193–2207, 2022, ISSN: 1476-5381.
Abstract | Links | BibTeX | Tags: 5-HT2R, Atopic dermatitis, Calcium imaging, Dorsal root ganglia, Glucosylsphingosine, TRPV4
@article{Sanjel2022b,
title = {Glucosylsphingosine evokes pruritus via activation of 5‐HT_{2A} receptor and TRPV4 in sensory neurons},
author = {Babina Sanjel and Bo‐Hyun Kim and Myung‐Hyun Song and Earl Carstens and Won‐Sik Shim},
doi = {10.1111/bph.15733},
issn = {1476-5381},
year = {2022},
date = {2022-05-00},
urldate = {2022-05-00},
journal = {British J Pharmacology},
volume = {179},
number = {10},
pages = {2193--2207},
publisher = {Wiley},
abstract = {Background and purpose
Glucosylsphingosine (GS), an endogenous sphingolipid, is highly accumulated in the epidermis of patients with atopic dermatitis (AD) due to abnormal ceramide metabolism. More importantly, GS can evoke scratching behaviours. However, the precise molecular mechanism by which GS induces pruritus has been elusive. Thus, the present study aimed to elucidate the molecular signalling pathway of GS, especially at the peripheral sensory neuronal levels.
Experimental approach
Calcium imaging was used to investigate the responses of HEK293T cells or mouse dorsal root ganglion (DRG) neurons to application of GS. Scratching behaviour tests were also performed with wild-type and Trpv4 knockout mice.
Key results
GS activated DRG neurons in a manner involving both the 5-HT2A receptor and TRPV4. Furthermore, GS-induced responses were significantly suppressed by various inhibitors, including ketanserin (5-HT2A receptor antagonist), YM254890 (Gαq/11 inhibitor), gallein (Gβγ complex inhibitor), U73122 (phospholipase C inhibitor), bisindolylmaleimide I (PKC inhibitor) and HC067047 (TRPV4 antagonist). Moreover, DRG neurons from Trpv4 knockout mice exhibited significantly reduced responses to GS. Additionally, GS-evoked scratching behaviours were greatly decreased by pretreatment with inhibitors of either 5-HT2A receptor or TRPV4. As expected, GS-evoked scratching behaviour was also significantly decreased in Trpv4 knockout mice.
Conclusion and implications
Overall, the present study provides evidence for a novel molecular signalling pathway for GS-evoked pruritus, which utilizes both 5-HT2A receptor and TRPV4 in mouse sensory neurons. Considering the high accumulation of GS in the epidermis of patients with AD, GS could be another pruritogen in patients with AD.},
keywords = {5-HT2R, Atopic dermatitis, Calcium imaging, Dorsal root ganglia, Glucosylsphingosine, TRPV4},
pubstate = {published},
tppubtype = {article}
}
Background and purpose
Glucosylsphingosine (GS), an endogenous sphingolipid, is highly accumulated in the epidermis of patients with atopic dermatitis (AD) due to abnormal ceramide metabolism. More importantly, GS can evoke scratching behaviours. However, the precise molecular mechanism by which GS induces pruritus has been elusive. Thus, the present study aimed to elucidate the molecular signalling pathway of GS, especially at the peripheral sensory neuronal levels.
Experimental approach
Calcium imaging was used to investigate the responses of HEK293T cells or mouse dorsal root ganglion (DRG) neurons to application of GS. Scratching behaviour tests were also performed with wild-type and Trpv4 knockout mice.
Key results
GS activated DRG neurons in a manner involving both the 5-HT2A receptor and TRPV4. Furthermore, GS-induced responses were significantly suppressed by various inhibitors, including ketanserin (5-HT2A receptor antagonist), YM254890 (Gαq/11 inhibitor), gallein (Gβγ complex inhibitor), U73122 (phospholipase C inhibitor), bisindolylmaleimide I (PKC inhibitor) and HC067047 (TRPV4 antagonist). Moreover, DRG neurons from Trpv4 knockout mice exhibited significantly reduced responses to GS. Additionally, GS-evoked scratching behaviours were greatly decreased by pretreatment with inhibitors of either 5-HT2A receptor or TRPV4. As expected, GS-evoked scratching behaviour was also significantly decreased in Trpv4 knockout mice.
Conclusion and implications
Overall, the present study provides evidence for a novel molecular signalling pathway for GS-evoked pruritus, which utilizes both 5-HT2A receptor and TRPV4 in mouse sensory neurons. Considering the high accumulation of GS in the epidermis of patients with AD, GS could be another pruritogen in patients with AD.
Glucosylsphingosine (GS), an endogenous sphingolipid, is highly accumulated in the epidermis of patients with atopic dermatitis (AD) due to abnormal ceramide metabolism. More importantly, GS can evoke scratching behaviours. However, the precise molecular mechanism by which GS induces pruritus has been elusive. Thus, the present study aimed to elucidate the molecular signalling pathway of GS, especially at the peripheral sensory neuronal levels.
Experimental approach
Calcium imaging was used to investigate the responses of HEK293T cells or mouse dorsal root ganglion (DRG) neurons to application of GS. Scratching behaviour tests were also performed with wild-type and Trpv4 knockout mice.
Key results
GS activated DRG neurons in a manner involving both the 5-HT2A receptor and TRPV4. Furthermore, GS-induced responses were significantly suppressed by various inhibitors, including ketanserin (5-HT2A receptor antagonist), YM254890 (Gαq/11 inhibitor), gallein (Gβγ complex inhibitor), U73122 (phospholipase C inhibitor), bisindolylmaleimide I (PKC inhibitor) and HC067047 (TRPV4 antagonist). Moreover, DRG neurons from Trpv4 knockout mice exhibited significantly reduced responses to GS. Additionally, GS-evoked scratching behaviours were greatly decreased by pretreatment with inhibitors of either 5-HT2A receptor or TRPV4. As expected, GS-evoked scratching behaviour was also significantly decreased in Trpv4 knockout mice.
Conclusion and implications
Overall, the present study provides evidence for a novel molecular signalling pathway for GS-evoked pruritus, which utilizes both 5-HT2A receptor and TRPV4 in mouse sensory neurons. Considering the high accumulation of GS in the epidermis of patients with AD, GS could be another pruritogen in patients with AD.