List of Publications (2011-Current)
2022
Sanjel, Babina; Shim, Won-Sik
The contribution of mouse models to understanding atopic dermatitis Journal Article
In: Biochemical Pharmacology, vol. 203, 2022, ISSN: 0006-2952.
Abstract | Links | BibTeX | Tags: Animal model, Atopic dermatitis, Itch
@article{Sanjel2022,
title = {The contribution of mouse models to understanding atopic dermatitis},
author = {Babina Sanjel and Won-Sik Shim},
doi = {10.1016/j.bcp.2022.115177},
issn = {0006-2952},
year = {2022},
date = {2022-09-00},
urldate = {2022-09-00},
journal = {Biochemical Pharmacology},
volume = {203},
publisher = {Elsevier BV},
abstract = {Atopic dermatitis (AD) is a dermatological disease accompanied by dry and cracked skin with severe pruritus. Although various therapeutic strategies have been introduced to alleviate AD, it remains challenging to cure the disorder. To achieve such a goal, understanding the pathophysiological mechanisms of AD is a prerequisite, requiring mouse models that properly reflect the AD phenotypes. Currently, numerous AD mouse models have been established, but each model has its own advantages and weaknesses. In this review, we categorized and summarized mouse models of AD and described their characteristics from a researcher’s perspective.},
keywords = {Animal model, Atopic dermatitis, Itch},
pubstate = {published},
tppubtype = {article}
}
Atopic dermatitis (AD) is a dermatological disease accompanied by dry and cracked skin with severe pruritus. Although various therapeutic strategies have been introduced to alleviate AD, it remains challenging to cure the disorder. To achieve such a goal, understanding the pathophysiological mechanisms of AD is a prerequisite, requiring mouse models that properly reflect the AD phenotypes. Currently, numerous AD mouse models have been established, but each model has its own advantages and weaknesses. In this review, we categorized and summarized mouse models of AD and described their characteristics from a researcher’s perspective.
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.
2019
Kim, Bo Hyun; Lee, Wook-Joo; Sanjel, Babina; Cho, Kyohee; Son, Youn Kyoung; Park, Hye Yoon; Kim, Sun Yeou; Shim, Won-Sik
Extracts of the leaves of Pyrus ussuriensis Maxim. Alleviate itch sensation via TSLP-dependent manner in mouse models of atopic dermatitis Journal Article
In: Physiology & Behavior, vol. 210, 2019, ISSN: 0031-9384.
Abstract | Links | BibTeX | Tags: Animal model, Atopic dermatitis, Calcium imaging, Itch, Scratching behavior, TSLP
@article{Kim2019,
title = {Extracts of the leaves of Pyrus ussuriensis Maxim. Alleviate itch sensation via TSLP-dependent manner in mouse models of atopic dermatitis},
author = {Bo Hyun Kim and Wook-Joo Lee and Babina Sanjel and Kyohee Cho and Youn Kyoung Son and Hye Yoon Park and Sun Yeou Kim and Won-Sik Shim},
doi = {10.1016/j.physbeh.2019.112624},
issn = {0031-9384},
year = {2019},
date = {2019-10-00},
urldate = {2019-10-00},
journal = {Physiology & Behavior},
volume = {210},
publisher = {Elsevier BV},
abstract = {Pyrus ussuriensis Maxim. commonly known as “Sandolbae” in Korean is a pear tree widely distributed across East Asia. Recent studies indicate that P. ussuriensis Maxim. leaves (PUL) have antipruritic effects. This study aimed to determine the effects of PUL extract and its fractions in decreasing the itch sensation and skin lesions in two distinct animal models of atopic dermatitis (AD) induced by dinitrofluorobenzene (DNFB) or house dust mite(HDM). Our results showed that the total ethanol extract of PUL decreased the scratching behavior in mice withDNFB- and HDM-induced AD. Moreover, the ethyl acetate fraction of PUL significantly improved the overallcondition of the mice with AD induced by HDM. Further, we used HEK293T cells that express receptors and ion channels for thymic stromal lymphopoietin (TSLP), a potent pruritogen for AD, to determine the mechanismsunderlying the antipruritic effects of PUL extract/fractions. Specific subfractions of the PUL strongly inhibited the increase in calcium levels induced by TSLP. In addition, the specific subfraction of PUL inhibited the TSLP-induced increase in calcium levels in cultured mouse dorsal root ganglia neurons. Thus, our results showed thatthe PUL extract could be effective for alleviating pruritus, and the antipruritic effects were exerted probably viathe inhibition of the TSLP pathway in peripheral sensory neurons governing the itch sensation in AD.},
keywords = {Animal model, Atopic dermatitis, Calcium imaging, Itch, Scratching behavior, TSLP},
pubstate = {published},
tppubtype = {article}
}
Pyrus ussuriensis Maxim. commonly known as “Sandolbae” in Korean is a pear tree widely distributed across East Asia. Recent studies indicate that P. ussuriensis Maxim. leaves (PUL) have antipruritic effects. This study aimed to determine the effects of PUL extract and its fractions in decreasing the itch sensation and skin lesions in two distinct animal models of atopic dermatitis (AD) induced by dinitrofluorobenzene (DNFB) or house dust mite(HDM). Our results showed that the total ethanol extract of PUL decreased the scratching behavior in mice withDNFB- and HDM-induced AD. Moreover, the ethyl acetate fraction of PUL significantly improved the overallcondition of the mice with AD induced by HDM. Further, we used HEK293T cells that express receptors and ion channels for thymic stromal lymphopoietin (TSLP), a potent pruritogen for AD, to determine the mechanismsunderlying the antipruritic effects of PUL extract/fractions. Specific subfractions of the PUL strongly inhibited the increase in calcium levels induced by TSLP. In addition, the specific subfraction of PUL inhibited the TSLP-induced increase in calcium levels in cultured mouse dorsal root ganglia neurons. Thus, our results showed thatthe PUL extract could be effective for alleviating pruritus, and the antipruritic effects were exerted probably viathe inhibition of the TSLP pathway in peripheral sensory neurons governing the itch sensation in AD.