Pub Date : 2024-09-07DOI: 10.1016/j.jid.2024.08.005
Nathaniel B Goldstein, Zachary B K Berk, Landon C Tomb, Junxiao Hu, Laura G Hoaglin, Dennis R Roop, Roni Adiri, Yonghua Zhuang, Juliana M Canosa, Paul Sanders, David A Norris, Karl Nocka, Amy Cha, Stanca A Birlea
Vitiligo is a common chronic autoimmune disease characterized by white macules and patches of the skin, having a negative impact on patients' life and without any definitive cure at present. Identification of new compounds to reverse depigmentation is therefore a pressing need for this disease. The pharmacologic compounds phosphodiesterase-4 inhibitors (PDE4is) are small molecules with immunomodulatory properties used for treatment of inflammatory dermatoses. PDE4is have shown repigmentation effects in patients with vitiligo, in some case reports. We characterized the proliferative and melanogenic potential of 2 known PDE4is-crisaborole and roflumilast-and of a more recently designed compound, PF-07038124. We used 2 in vitro model systems-the primary human melanocyte culture and a 3-dimensional cocultured skin model (MelanoDerm)-with an exploratory testing platform composed of complementary assays (spectrophotometry, melanin and proliferation assays, immunostaining, Fontana-Masson staining, RT-qPCR, western blot, and whole-transcriptome RNA sequencing). We identified that treatment with PDE4is was associated with increased melanocyte proliferation and melanization in both in vitro models and with increase in the melanogenic genes and proteins expression in cultured melanocytes. These effects were found to be enhanced by addition of α-melanocyte-stimulating hormone. Our findings support the further evaluation of PDE4is with or without α-melanocyte-stimulating hormone agonists in vitiligo trials.
{"title":"Phosphodiesterase-4 Inhibitors Increase Pigment Cell Proliferation and Melanization in Cultured Melanocytes and within a 3-Dimensional Skin Equivalent Model.","authors":"Nathaniel B Goldstein, Zachary B K Berk, Landon C Tomb, Junxiao Hu, Laura G Hoaglin, Dennis R Roop, Roni Adiri, Yonghua Zhuang, Juliana M Canosa, Paul Sanders, David A Norris, Karl Nocka, Amy Cha, Stanca A Birlea","doi":"10.1016/j.jid.2024.08.005","DOIUrl":"10.1016/j.jid.2024.08.005","url":null,"abstract":"<p><p>Vitiligo is a common chronic autoimmune disease characterized by white macules and patches of the skin, having a negative impact on patients' life and without any definitive cure at present. Identification of new compounds to reverse depigmentation is therefore a pressing need for this disease. The pharmacologic compounds phosphodiesterase-4 inhibitors (PDE4is) are small molecules with immunomodulatory properties used for treatment of inflammatory dermatoses. PDE4is have shown repigmentation effects in patients with vitiligo, in some case reports. We characterized the proliferative and melanogenic potential of 2 known PDE4is-crisaborole and roflumilast-and of a more recently designed compound, PF-07038124. We used 2 in vitro model systems-the primary human melanocyte culture and a 3-dimensional cocultured skin model (MelanoDerm)-with an exploratory testing platform composed of complementary assays (spectrophotometry, melanin and proliferation assays, immunostaining, Fontana-Masson staining, RT-qPCR, western blot, and whole-transcriptome RNA sequencing). We identified that treatment with PDE4is was associated with increased melanocyte proliferation and melanization in both in vitro models and with increase in the melanogenic genes and proteins expression in cultured melanocytes. These effects were found to be enhanced by addition of α-melanocyte-stimulating hormone. Our findings support the further evaluation of PDE4is with or without α-melanocyte-stimulating hormone agonists in vitiligo trials.</p>","PeriodicalId":94239,"journal":{"name":"The Journal of investigative dermatology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142057733","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-06DOI: 10.1016/j.jid.2024.06.1292
Marjaana Häyrinen, Hanna-Riikka Teppo, Liisa Väkevä, Annamari Ranki, Henry J Barton, Katja Porvari, Jenni Kiiskilä, Milla E L Kuusisto, Hanne Kuitunen, Siria Lemma, Helka Sahi, Kirsi-Maria Haapasaari, Outi Kuittinen
{"title":"Tumor RNA Sequencing Identifies a Group of Patients with Mycosis Fungoides with Failure of Skin-Directed Therapies.","authors":"Marjaana Häyrinen, Hanna-Riikka Teppo, Liisa Väkevä, Annamari Ranki, Henry J Barton, Katja Porvari, Jenni Kiiskilä, Milla E L Kuusisto, Hanne Kuitunen, Siria Lemma, Helka Sahi, Kirsi-Maria Haapasaari, Outi Kuittinen","doi":"10.1016/j.jid.2024.06.1292","DOIUrl":"10.1016/j.jid.2024.06.1292","url":null,"abstract":"","PeriodicalId":94239,"journal":{"name":"The Journal of investigative dermatology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142157083","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-06DOI: 10.1016/j.jid.2024.08.016
Young In Lee, Yohan Yang, Seoyoon Ham, Jung Eun Shim, Sang Gyu Lee, Si-Hyung Lee, Tae-Gyun Kim, Won Jai Lee, Do-Young Kim, Ju Hee Lee
{"title":"Heterogeneity in keloid scars: influence of mechanical stretching on keloids arising from different anatomical sites.","authors":"Young In Lee, Yohan Yang, Seoyoon Ham, Jung Eun Shim, Sang Gyu Lee, Si-Hyung Lee, Tae-Gyun Kim, Won Jai Lee, Do-Young Kim, Ju Hee Lee","doi":"10.1016/j.jid.2024.08.016","DOIUrl":"https://doi.org/10.1016/j.jid.2024.08.016","url":null,"abstract":"","PeriodicalId":94239,"journal":{"name":"The Journal of investigative dermatology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142157082","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-05DOI: 10.1016/j.jid.2024.06.1282
Elsabe Cloete, Malebogo N Ngoepe, Ernesto Ismail, Nonhlanhla P Khumalo
{"title":"Weak Hydrogen Bonds in Temporary Shape Changes of Curly Human Hair Fibers: Preliminary Evidence.","authors":"Elsabe Cloete, Malebogo N Ngoepe, Ernesto Ismail, Nonhlanhla P Khumalo","doi":"10.1016/j.jid.2024.06.1282","DOIUrl":"10.1016/j.jid.2024.06.1282","url":null,"abstract":"","PeriodicalId":94239,"journal":{"name":"The Journal of investigative dermatology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141604725","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-05DOI: 10.1016/j.jid.2024.07.009
Sarah G Brooks, Rami H Mahmoud, Rachel R Lin, Joachim W Fluhr, Gil Yosipovitch
The acid mantle concept refers to the buffer system located in the upper stratum corneum of the skin. By sustaining an acidic environment, the acid mantle contributes to the regulation of the microbiome, structural stability, and inflammation. Skin pH is pivotal in maintaining the integrity of the epidermal barrier. Shifts in pH can disrupt barrier properties, and recent studies have emphasized its impact on dermatologic disease processes. This review explores the complex relationship of mechanisms through which skin pH impacts dermatologic pathologies. Furthermore, we highlight the promising potential of pH-targeted therapies for advancing the management of skin conditions.
{"title":"The Skin Acid Mantle: An Update on Skin pH.","authors":"Sarah G Brooks, Rami H Mahmoud, Rachel R Lin, Joachim W Fluhr, Gil Yosipovitch","doi":"10.1016/j.jid.2024.07.009","DOIUrl":"https://doi.org/10.1016/j.jid.2024.07.009","url":null,"abstract":"<p><p>The acid mantle concept refers to the buffer system located in the upper stratum corneum of the skin. By sustaining an acidic environment, the acid mantle contributes to the regulation of the microbiome, structural stability, and inflammation. Skin pH is pivotal in maintaining the integrity of the epidermal barrier. Shifts in pH can disrupt barrier properties, and recent studies have emphasized its impact on dermatologic disease processes. This review explores the complex relationship of mechanisms through which skin pH impacts dermatologic pathologies. Furthermore, we highlight the promising potential of pH-targeted therapies for advancing the management of skin conditions.</p>","PeriodicalId":94239,"journal":{"name":"The Journal of investigative dermatology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142147268","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-04DOI: 10.1016/j.jid.2024.07.034
Eunbi Yu, Sae Woong Oh, See-Hyoung Park, Kitae Kwon, Su Bin Han, Su Hyun Kang, Jung Hyun Lee, Heejun Ha, Donghoon Yoon, Eunsun Jung, Minkyung Song, Jae Youl Cho, Jongsung Lee
Blue light, a high-energy radiation in the visible light spectrum, was recently reported to induce skin pigmentation. In this study, we investigated the involvement of TRPV1-mediated signaling along with OPN3 in blue light-induced melanogenesis as well as its signaling pathway. Operating downstream target of OPN3 in blue light-induced melanogenesis, blue light activated TRPV1 and upregulated its expression, resulting in calcium influx. Calcium ion induced the activation of calcium/calmodulin-dependent protein kinase II and MAPK. It also downregulated clusterin expression, leading to the nuclear translocation of PAX3, ultimately affecting melanin synthesis. In addition, blue light interfered with autophagy-mediated regulation of melanosomes by decreasing not only the interaction between clusterin and LC3B but the expression of activating transcription factor family. These findings demonstrate that the pigmenting effects of blue light are mediated by calcium/calmodulin-dependent protein kinase II- and MAPK-mediated signaling as well as clusterin-dependent inhibition of autophagy through OPN3-TRPV1-calcium influx, suggesting, to our knowledge, a previously unreported signaling pathway through which blue light regulates melanocyte biology. Furthermore, these results suggest that TRPV1 and clusterin could be potential therapeutic targets for blue light-induced pigmentation due to prolonged exposure to blue light.
{"title":"The Pigmentation of Blue Light Is Mediated by Both Melanogenesis Activation and Autophagy Inhibition through OPN3-TRPV1.","authors":"Eunbi Yu, Sae Woong Oh, See-Hyoung Park, Kitae Kwon, Su Bin Han, Su Hyun Kang, Jung Hyun Lee, Heejun Ha, Donghoon Yoon, Eunsun Jung, Minkyung Song, Jae Youl Cho, Jongsung Lee","doi":"10.1016/j.jid.2024.07.034","DOIUrl":"10.1016/j.jid.2024.07.034","url":null,"abstract":"<p><p>Blue light, a high-energy radiation in the visible light spectrum, was recently reported to induce skin pigmentation. In this study, we investigated the involvement of TRPV1-mediated signaling along with OPN3 in blue light-induced melanogenesis as well as its signaling pathway. Operating downstream target of OPN3 in blue light-induced melanogenesis, blue light activated TRPV1 and upregulated its expression, resulting in calcium influx. Calcium ion induced the activation of calcium/calmodulin-dependent protein kinase II and MAPK. It also downregulated clusterin expression, leading to the nuclear translocation of PAX3, ultimately affecting melanin synthesis. In addition, blue light interfered with autophagy-mediated regulation of melanosomes by decreasing not only the interaction between clusterin and LC3B but the expression of activating transcription factor family. These findings demonstrate that the pigmenting effects of blue light are mediated by calcium/calmodulin-dependent protein kinase II- and MAPK-mediated signaling as well as clusterin-dependent inhibition of autophagy through OPN3-TRPV1-calcium influx, suggesting, to our knowledge, a previously unreported signaling pathway through which blue light regulates melanocyte biology. Furthermore, these results suggest that TRPV1 and clusterin could be potential therapeutic targets for blue light-induced pigmentation due to prolonged exposure to blue light.</p>","PeriodicalId":94239,"journal":{"name":"The Journal of investigative dermatology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142147267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-03DOI: 10.1016/j.jid.2024.03.049
Hristijan Goreski, Dusko Ilic, Vincent Flacher, Ellen van den Bogaard, Christina Guttmann-Gruber, Reiko J Tanaka, Gülcihan Gülseren, Christophe Marquette, Joachim Fluhr, Viviane Filor, Serghei Sprincean, Sandrine Dubrac
{"title":"NETSKINMODELS: A European Network for Skin Engineering and Modeling.","authors":"Hristijan Goreski, Dusko Ilic, Vincent Flacher, Ellen van den Bogaard, Christina Guttmann-Gruber, Reiko J Tanaka, Gülcihan Gülseren, Christophe Marquette, Joachim Fluhr, Viviane Filor, Serghei Sprincean, Sandrine Dubrac","doi":"10.1016/j.jid.2024.03.049","DOIUrl":"https://doi.org/10.1016/j.jid.2024.03.049","url":null,"abstract":"","PeriodicalId":94239,"journal":{"name":"The Journal of investigative dermatology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142127799","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-03DOI: 10.1016/j.jid.2024.08.013
Daniel C Stewart, Becky K Brisson, William K Yen, Yuchen Liu, Chao Wang, Gordon Ruthel, Donald Gullberg, Robert L Mauck, Malcolm Maden, Lin Han, Susan W Volk
Postnatal cutaneous wound healing is characterized by development of a collagen-rich scar lacking the architecture and functional integrity of unwounded tissue. Directing cell behaviors to efficiently heal wounds while minimizing scar formation remains a major wound management goal. In this study, we demonstrate type III collagen (COL3) as a critical regulator of re-epithelialization and scar formation during healing of COL3-enriched, regenerative (Acomys), scar-permissive (CD-1 Mus and wild-type Col3B6/B6 mice) and COL3-deficient, scar-promoting (Col3F/F, a murine conditional knockdown model) cutaneous wound models. We define a scar-permissive fibrillar collagen architecture signature characterized by elongated and anisotropically aligned collagen fibers that is dose-dependently suppressed by COL3. Furthermore, loss of COL3 alters how cells interpret their microenvironment-their mechanoperception-such that COL3-deficient cells display mechanically active phenotypes in the absence of increased microenvironmental stiffness through the upregulation and engagement of the profibrotic integrin α11. Further understanding COL3's role in regulating matrix architecture and mechanoresponses may inform clinical strategies that harness proregenerative mechanisms.
{"title":"Type III Collagen Regulates Matrix Architecture and Mechanosensing during Wound Healing.","authors":"Daniel C Stewart, Becky K Brisson, William K Yen, Yuchen Liu, Chao Wang, Gordon Ruthel, Donald Gullberg, Robert L Mauck, Malcolm Maden, Lin Han, Susan W Volk","doi":"10.1016/j.jid.2024.08.013","DOIUrl":"10.1016/j.jid.2024.08.013","url":null,"abstract":"<p><p>Postnatal cutaneous wound healing is characterized by development of a collagen-rich scar lacking the architecture and functional integrity of unwounded tissue. Directing cell behaviors to efficiently heal wounds while minimizing scar formation remains a major wound management goal. In this study, we demonstrate type III collagen (COL3) as a critical regulator of re-epithelialization and scar formation during healing of COL3-enriched, regenerative (Acomys), scar-permissive (CD-1 Mus and wild-type Col3<sup>B6/B6</sup> mice) and COL3-deficient, scar-promoting (Col3<sup>F/F</sup>, a murine conditional knockdown model) cutaneous wound models. We define a scar-permissive fibrillar collagen architecture signature characterized by elongated and anisotropically aligned collagen fibers that is dose-dependently suppressed by COL3. Furthermore, loss of COL3 alters how cells interpret their microenvironment-their mechanoperception-such that COL3-deficient cells display mechanically active phenotypes in the absence of increased microenvironmental stiffness through the upregulation and engagement of the profibrotic integrin α11. Further understanding COL3's role in regulating matrix architecture and mechanoresponses may inform clinical strategies that harness proregenerative mechanisms.</p>","PeriodicalId":94239,"journal":{"name":"The Journal of investigative dermatology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142142223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-03DOI: 10.1016/j.jid.2024.08.014
Jasson Makkar, Jorge Flores, Mason Matich, Tommy T Duong, Sean M Thompson, Yiqing Du, Isabelle Busch, Quan M Phan, Qing Wang, Kristen Delevich, Liam Broughton-Neiswanger, Iwona M Driskell, Ryan R Driskell
Hair quality is an important indicator of health in humans and other animals. Current approaches to assess hair quality are generally nonquantitative or are low throughput owing to technical limitations of splitting hairs. We developed a deep learning-based computer vision approach for the high-throughput quantification of individual hair fibers at a high resolution. Our innovative computer vision tool can distinguish and extract overlapping fibers for quantification of multivariate features, including length, width, and color, to generate single-hair phenomes of diverse conditions across the lifespan of mice. Using our tool, we explored the effects of hormone signaling, genetic modifications, and aging on hair follicle output. Our analyses revealed hair phenotypes resultant of endocrinological, developmental, and aging-related alterations in the fur coats of mice. These results demonstrate the efficacy of our deep hair phenomics tool for characterizing factors that modulate the hair follicle and developing, to our knowledge, previously unreported diagnostic methods for detecting disease through the hair fiber. Finally, we have generated a searchable, interactive web tool for the exploration of our hair fiber data at skinregeneration.org.
{"title":"Deep Hair Phenomics: Implications in Endocrinology, Development, and Aging.","authors":"Jasson Makkar, Jorge Flores, Mason Matich, Tommy T Duong, Sean M Thompson, Yiqing Du, Isabelle Busch, Quan M Phan, Qing Wang, Kristen Delevich, Liam Broughton-Neiswanger, Iwona M Driskell, Ryan R Driskell","doi":"10.1016/j.jid.2024.08.014","DOIUrl":"10.1016/j.jid.2024.08.014","url":null,"abstract":"<p><p>Hair quality is an important indicator of health in humans and other animals. Current approaches to assess hair quality are generally nonquantitative or are low throughput owing to technical limitations of splitting hairs. We developed a deep learning-based computer vision approach for the high-throughput quantification of individual hair fibers at a high resolution. Our innovative computer vision tool can distinguish and extract overlapping fibers for quantification of multivariate features, including length, width, and color, to generate single-hair phenomes of diverse conditions across the lifespan of mice. Using our tool, we explored the effects of hormone signaling, genetic modifications, and aging on hair follicle output. Our analyses revealed hair phenotypes resultant of endocrinological, developmental, and aging-related alterations in the fur coats of mice. These results demonstrate the efficacy of our deep hair phenomics tool for characterizing factors that modulate the hair follicle and developing, to our knowledge, previously unreported diagnostic methods for detecting disease through the hair fiber. Finally, we have generated a searchable, interactive web tool for the exploration of our hair fiber data at skinregeneration.org.</p>","PeriodicalId":94239,"journal":{"name":"The Journal of investigative dermatology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142142266","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The mammalian epidermis is a structurally complex tissue that serves critical barrier functions, safeguarding the organism from the external milieu. The development of the epidermis is governed by sophisticated regulatory processes. However, the precise mechanism maintaining epidermal homeostasis remains incompletely elucidated. Recent studies have identified Paxbp1, an evolutionarily conserved protein, as being involved in the developmental regulation of various cells, tissues, and organs. Nonetheless, its role in skin development has not been explored. In this study, we report that the targeted deletion of Paxbp1 in epidermal keratinocytes mediated by keratin 14-Cre leads to severe disruption in skin architecture. Mice deficient in Paxbp1 exhibited a substantially reduced epidermal thickness and pronounced separation at the dermal-epidermal junction upon birth. Mechanistically, we demonstrate that the absence of Paxbp1 hinders cellular proliferation, marked by a halt in cell cycle transition, suppressed gene expression of proliferation, and a compromised DNA replication pathway in basal keratinocytes, resulting in the thinning of the skin epidermis. Moreover, molecules and pathways associated with hemidesmosome assembly were impaired in Paxbp1-deficient keratinocytes, culminating in the detachment of the skin epidermal layer. Therefore, our study highlights an indispensable role of Paxbp1 in the maintenance of epidermal homeostasis.
{"title":"Paxbp1 Is Indispensable for the Maintenance of Epidermal Homeostasis.","authors":"Cong Huang, Shenglin Liu, Wenting Li, Shizheng Zhao, Xuanyao Ren, Fan Zhuo, Kaoyuan Zhang, Xiahong Li, Jingwen Wu, Zimo Zhu, Chao Chen, Wei Zhang, Bo Yu","doi":"10.1016/j.jid.2024.08.012","DOIUrl":"10.1016/j.jid.2024.08.012","url":null,"abstract":"<p><p>The mammalian epidermis is a structurally complex tissue that serves critical barrier functions, safeguarding the organism from the external milieu. The development of the epidermis is governed by sophisticated regulatory processes. However, the precise mechanism maintaining epidermal homeostasis remains incompletely elucidated. Recent studies have identified Paxbp1, an evolutionarily conserved protein, as being involved in the developmental regulation of various cells, tissues, and organs. Nonetheless, its role in skin development has not been explored. In this study, we report that the targeted deletion of Paxbp1 in epidermal keratinocytes mediated by keratin 14-Cre leads to severe disruption in skin architecture. Mice deficient in Paxbp1 exhibited a substantially reduced epidermal thickness and pronounced separation at the dermal-epidermal junction upon birth. Mechanistically, we demonstrate that the absence of Paxbp1 hinders cellular proliferation, marked by a halt in cell cycle transition, suppressed gene expression of proliferation, and a compromised DNA replication pathway in basal keratinocytes, resulting in the thinning of the skin epidermis. Moreover, molecules and pathways associated with hemidesmosome assembly were impaired in Paxbp1-deficient keratinocytes, culminating in the detachment of the skin epidermal layer. Therefore, our study highlights an indispensable role of Paxbp1 in the maintenance of epidermal homeostasis.</p>","PeriodicalId":94239,"journal":{"name":"The Journal of investigative dermatology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142142222","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}