Experimental AnimalsPub Date : 2026-10-15Epub Date: 2026-05-21DOI: 10.1538/expanim.26-0048
Haiyang Sun, Rujiao Jiang, Jingjing Jing, Xinying Wang, Ning Wang, Meihua Guo, Ce Tang
{"title":"Artesunate ameliorates experimental colitis by suppressing intestinal inflammation and modulating the gut microbiota.","authors":"Haiyang Sun, Rujiao Jiang, Jingjing Jing, Xinying Wang, Ning Wang, Meihua Guo, Ce Tang","doi":"10.1538/expanim.26-0048","DOIUrl":"10.1538/expanim.26-0048","url":null,"abstract":"<p><p>Artesunate (ART) is a semi-synthetic derivative of artemisinin with well-established antimalarial activity. In this study, we demonstrate that ART treatment markedly attenuates disease severity in dextran sulfate sodium (DSS)-induced colitis. ART significantly reduces the accumulation of inflammatory neutrophils, monocytes, Th17 cells, and IL-17-producing innate lymphoid cells (ILCs) and γδT cells in the colon, accompanied by suppression of pro-inflammatory gene expression, including Tnf, Il6, and Il1b, and upregulation of anti-inflammatory mediators such as Tgfb and Il10. In parallel, ART restores the expression of intestinal tight junction proteins zonula occludens-1 (ZO-1) and claudin-1, indicating improved epithelial barrier integrity. ART treatment inhibits the IL-17 production from both Th17 cells and other lymphocytes. ART also reshapes the gut microbiota, which contributes to protection against DSS-induced colitis. Notably, mesalazine co-treatment with ART augmented its protective efficacy against DSS-induced colitis. Collectively, these findings identify ART as a potent modulator of intestinal inflammation and barrier function, highlighting its therapeutic potential for mucosal inflammatory diseases.</p>","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":" ","pages":"439-453"},"PeriodicalIF":2.0,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13669690/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147981430","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Experimental AnimalsPub Date : 2026-10-15Epub Date: 2026-04-29DOI: 10.1538/expanim.26-0047
Limin Li, Cai Zhang, Lu Chen, Wenchao Yao, Xiaoli Hou, Zhengxiao Li, Faming Tian
{"title":"Keratinocyte-specific STAT3 knockout attenuates imiquimod-induced psoriasiform phenotype in mice.","authors":"Limin Li, Cai Zhang, Lu Chen, Wenchao Yao, Xiaoli Hou, Zhengxiao Li, Faming Tian","doi":"10.1538/expanim.26-0047","DOIUrl":"10.1538/expanim.26-0047","url":null,"abstract":"<p><p>Signal transducer and activator of transcription 3 (STAT3) is critical in psoriasis, but keratinocyte-derived STAT3 remains unclear. This study investigated the effect of keratinocyte-specific STAT3 knockout on imiquimod (IMQ)-induced psoriasis-like dermatitis. Keratinocyte-specific STAT3 knockout (Conditional knockout, cKO) mice and littermate controls (LC) received daily topical 5% IMQ to induce psoriasis-like lesions. Lesion severity was assessed by PASI score, histopathology by H&E staining, and systemic inflammation by spleen index and serum chemokine C-X-C motif ligand (CXCL1), chemokine C-C motif ligand 20 (CCL20), and IL-22 levels (ELISA). Skin expression of inflammation, chemokine, and STAT3 pathway related factors was examined by immunohistochemistry (IHC), real-time quantitative polymerase chain reaction (qRT-PCR), and western blot. In vitro, IL-17A-stimulated HaCaT cells were used with siRNA-mediated STAT3 knockdown; changes in STAT3 signaling and downstream factors were assessed by qRT-PCR and Western blot. In vivo, keratinocyte-specific STAT3 knockout significantly alleviated IMQ-induced skin lesions, reduced PASI score, improved barrier function, decreased spleen index, and lowered serum CXCL1, CCL20, and IL-22. It also suppressed IL-22, CXCL1, and CCL20 expression in skin and inhibited STAT3 activation. In vitro, IL-17A increased STAT3 phosphorylation, which was blocked by STAT3 knockdown, along with suppression of IL-22 and CXCL1 upregulation.</p>","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":" ","pages":"405-416"},"PeriodicalIF":2.0,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13669692/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147766559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A viral FLIP protein, E8, exogenously-expressed in the mesenchymal lineage of mice leads to bone malformations, lipoatrophy, and muscular atrophy.","authors":"Kazuhiro Sakamaki, Nobuyuki Yajima, Yasumasa Okazaki, Taku Toriumi, Masaki Honda, Shinya Toyokuni, Yoshinori Arai","doi":"10.1538/expanim.26-0074","DOIUrl":"10.1538/expanim.26-0074","url":null,"abstract":"<p><p>The equine herpes virus 2, E8 protein is a member of the viral FLIP family, and as such, it is a potent inhibitor of death receptor-induced apoptosis in cultured cells. To extend our study of the effects of E8 to animals, we generated a mouse model in which the progeny of a cross between two transgenic mice conditionally express E8 under the control of the collagen type I α2 chain (Col1α2) promoter, allowing us to monitor and characterize the effects of E8 expression in the mesenchymal cell lineage. We observed growth defects associated with irregular bone formation during development. In addition, adult animals exhibited both lipoatrophy-like and muscular atrophy-like symptoms. These abnormal phenotypes likely arise from incomplete differentiation of mesenchymal stem cells (MSCs). To examine this hypothesis in more detail, we expressed E8 in the mouse MSC line C3H10T1/2 and performed a microarray analysis. Factors such as Nov/CCN3, STEAP4, and Ankrd1/CARP, which are involved in differentiation from MSCs to osteoblasts, adipocytes and myoblasts were affected. Taken together, our results demonstrate that the constitutive expression of herpesvirus gene products in the mesenchymal progenitors affects differentiation into multiple cell lineages.</p>","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":" ","pages":"485-497"},"PeriodicalIF":2.0,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13669693/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148389867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Tensin2 deficiency transiently accelerates early-phase regenerative myofiber growth following cardiotoxin-induced injury in mice.","authors":"Marina Miyaki, Yusuke Komiya, Minori Nakada, Kensei Noguchi, Issei Yokoyama, Takahiro Suzuki, Koichi Ojima, Keizo Arihara, Nobuya Sasaki","doi":"10.1538/expanim.26-0039","DOIUrl":"10.1538/expanim.26-0039","url":null,"abstract":"<p><p>Tensin2 (TNS2) is a focal adhesion-associated protein that can negatively regulate insulin/insulin-like growth factor 1 (IGF-1) signaling, but its role in skeletal muscle regeneration remains unclear. To address this, we analyzed a TNS2-related immunoreactive signal detected with an anti-phospho-TNS2 (Tyr483) antibody during C2C12 myogenic differentiation and in a cardiotoxin (CTX)-induced tibialis anterior (TA) injury model, and assessed regeneration in Tns2<sup>nph</sup> mutant mice. Under basal conditions, Tns2<sup>nph</sup> mice showed no obvious abnormalities in muscle histology, myofiber size, or phosphorylation of Akt and p70 ribosomal protein S6 kinase (p70S6K), a canonical downstream effector of mTORC1 signaling, compared with wild-type (WT) mice, although the soleus muscle/body weight ratio was slightly increased. In C2C12 cells, the anti-phospho-TNS2 (Tyr483)-reactive signal was stronger during proliferation than during differentiation. In vivo, this signal increased transiently during the early phase of CTX-mediated regeneration. After injury, Tns2<sup>nph</sup> mice showed a greater number of centrally nucleated fibers at day 4, larger myofibers at day 7, and a higher TA muscle/body weight ratio at day 15. In addition, phosphorylation of p70S6K was increased in regenerating muscle in Tns2<sup>nph</sup> mice. These findings suggest that TNS2-related signaling may act as a context-dependent modulator of regenerative myofiber growth, possibly through augmented anabolic signaling during early regeneration.</p>","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":" ","pages":"454-463"},"PeriodicalIF":2.0,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13669697/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147980913","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Pitfalls in lung subtraction CT: delayed contrast acquisition causes underestimation of pulmonary perfusion in a canine model.","authors":"Kentaro Yamazaki, Kosei Teraoka, Masayoshi Nagakawa, Chiharu Ito, Akari Taniguchi, Kodai Tashiro, Kazuya Kushida, Kija Lee, Yuki Hoshino, Yukiko Sassa-O'Brien, Miori Kishimoto","doi":"10.1538/expanim.26-0160","DOIUrl":"https://doi.org/10.1538/expanim.26-0160","url":null,"abstract":"<p><p>Lung subtraction computed tomography (LSCT), assessing pulmonary perfusion by subtracting non-contrast-enhanced images from contrast-enhanced images, may underestimate pulmonary perfusion when contrast-enhanced image acquisition is delayed. This study aimed to evaluate the effects of delayed acquisition of contrast-enhanced images on the LSCT assessment of pulmonary perfusion and identify indicators of sufficient contrast enhancement for LSCT generation using healthy beagles. Five beagles underwent continuous cine computed tomography (CT) for 30 s. After the second scan, iodixanol was intravenously administered. LSCT images were generated by subtracting pre-contrast images from contrast-enhanced images. On LSCT images, lung CT values and the percentage of areas with CT values of 0-20 HU were measured at the pulmonary trunk and tracheal bifurcation levels when the lung CT value on LSCT images was the highest and at 1.5 and 3.0 s thereafter. Pulmonary trunk CT values and pulmonary trunk-to-aorta (Pa/Ao) CT value ratios were recorded. Lung CT values decreased significantly over time, whereas the percentages of 0-20 HU areas increased. Pulmonary trunk CT values were associated positively with lung CT values and negatively with the percentages of 0-20 HU areas at both slice levels. Pa/Ao ratios showed similar significant associations at the pulmonary trunk level but not at the tracheal bifurcation level. In conclusion, delayed acquisition resulted in underestimation of pulmonary perfusion on LSCT images. These findings highlight the importance of appropriate acquisition timing. Pa/Ao ratios might indicate whether contrast enhancement is sufficient for LSCT generation.</p>","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149179809","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Experimental AnimalsPub Date : 2026-10-15Epub Date: 2026-05-13DOI: 10.1538/expanim.26-0023
Kinari Matsumoto, Akihiro Kuno, Seiya Mizuno
{"title":"AltEx-BE: a tool for designing splice-site-targeting gRNAs for base editing-mediated exon skipping with exon-level annotations in diverse experimental animals.","authors":"Kinari Matsumoto, Akihiro Kuno, Seiya Mizuno","doi":"10.1538/expanim.26-0023","DOIUrl":"10.1538/expanim.26-0023","url":null,"abstract":"<p><p>Pre-mRNA splicing is a conserved post-transcriptional regulatory process in eukaryotes, and mis-splicing is associated with numerous diseases. Therefore, experimentally induced exon skipping provides an important strategy for exon-level analysis of gene function. Exons can be broadly classified by their usage patterns across transcripts: some are shared by all transcripts, whereas others are selectively used across transcripts. Skipping the former affects all transcripts and often results in gene-level effects, while skipping the latter reflects functional diversity across transcripts. Therefore, considering characteristics of target exons is important to enhance interpretability of exon-level functional analysis. Recent advances in base editing enable exon skipping by introducing point mutations at splice sites, providing an approach for exon-level analysis. Accordingly, several guide RNA (gRNA) design tools have been developed for the purpose of inducing exon skipping. However, existing tools do not provide exon-level properties, including exon usage patterns, reading frame, and coding status. As a result, selecting target exons appropriate for specific research objectives remains difficult. Here we developed AltEx-BE, an automated gRNA design tool for base editing-mediated splice site disruption. AltEx-BE uses transcript annotations and reference genome sequences as inputs to classify each exon by usage pattern and to generate gRNA candidates compatible with several base editing tools. The tool also provides annotations, including coding status, to facilitate interpretation of outcomes of exon skipping. The tool promotes base editing-mediated exon skipping experiments across model organisms and enhances the interpretability of experimental outcomes.</p>","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":" ","pages":"429-438"},"PeriodicalIF":2.0,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13669695/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147927914","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Experimental AnimalsPub Date : 2026-10-15Epub Date: 2026-05-09DOI: 10.1538/expanim.26-0002
Yi Luo, Mio Kobayashi, Di Zhang, Yosuke Ono, Osamu Yoshino, Masahiko Kanehira
{"title":"Resveratrol alleviates endometriosis via restoration of hypoxic milieu and inhibition of autoantibody deposition.","authors":"Yi Luo, Mio Kobayashi, Di Zhang, Yosuke Ono, Osamu Yoshino, Masahiko Kanehira","doi":"10.1538/expanim.26-0002","DOIUrl":"10.1538/expanim.26-0002","url":null,"abstract":"<p><p>Endometriosis, a chronic disease that affects about 10% of women of reproductive age, is characterized by severe pain and growth of endometrium-like tissues outside the uteri. Although several theories have been advanced for the cause of endometriosis, no theory fully explains why endometriosis occurs. For this study, we strove to elucidate a new mechanism of endometriosis leading to establishment of a new therapeutic strategy for its treatment. In our murine endometriosis model, a marked hypoxic state was induced in the peritoneal cavity, as indicated by increased expression of HIF-1α in peritoneal exudate cells. Moreover, innate immune response, such as TLR4 and IL-1β expression, was upregulated. To restore the hypoxic milieu in endometriosis, we chose resveratrol (RSV), a natural polyphenolic compound, as a hypoxia-reducing agent. As expected, RSV administration decreased the number of HIF-1α-positive cells. Furthermore, RSV administration reduced the size and weight of endometriotic lesions significantly. However, RSV administration did not change TLR4 and IL-1β expression levels in peritoneal exudate cells. In the process of seeking mechanisms of endometriosis other than TLR4-dependent and IL-1β-dependent pathways, we detected autoantibody deposition in endometriotic lesions. In endometriotic lesions from RSV-administered mice, accumulation of autoantibodies was inhibited compared to a control group. As described herein, we proposed a new concept by which autoantibody deposition can cause endometriosis, raising the possibility of RSV as a promising therapeutic option for endometriosis.</p>","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":" ","pages":"417-428"},"PeriodicalIF":2.0,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13669691/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147867405","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Experimental AnimalsPub Date : 2026-10-15Epub Date: 2026-06-23DOI: 10.1538/expanim.26-0019
Xianfeng Wu, Shujuan Gao, Yuwei Zou, Chunyong Yang, Zhiyong Yang, Xiaobo Wang, Yujie Li, Ziyang Zeng, Bin Yi
{"title":"A novel non-transecting ligation technique for clinically mimetic cholestatic cirrhosis in rats.","authors":"Xianfeng Wu, Shujuan Gao, Yuwei Zou, Chunyong Yang, Zhiyong Yang, Xiaobo Wang, Yujie Li, Ziyang Zeng, Bin Yi","doi":"10.1538/expanim.26-0019","DOIUrl":"10.1538/expanim.26-0019","url":null,"abstract":"<p><p>The conventional common bile duct ligation (CBDL) model suffers from high postoperative mortality (frequently exceeding 50%), which severely limits longitudinal monitoring of disease progression and complications such as hepatopulmonary syndrome (HPS). We developed an improved CBDL (MCBDL) to preserve the continuity of bile duct, and compared MCBDL (n=40) with traditional CBDL (n=40) and sham operation (n=10) within 42 days. MCBDL captures cirrhosis and extrahepatic organ injury while significantly improving survival (72.5% vs. 45%, P=0.003) and attenuating systemic inflammation (IL-6: 117 ± 11 vs. 153 ± 26 pg/ml, P=0.047). Scanning electron microscopy revealed persistent secretory activity in ligated epithelia of both groups, but only CBDL permitted leakage from isolated stumps, creating a pathogenic cycle driving mortality. By preserving ductal continuity, MCBDL is associated with significantly reduced mortality while maintaining the hallmark features of cholestatic cirrhosis (METAVIR F4) and HPS-related extrahepatic complications, providing a stable platform for mechanistic studies.</p>","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":" ","pages":"464-473"},"PeriodicalIF":2.0,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13669689/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148316546","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Experimental AnimalsPub Date : 2026-10-15Epub Date: 2026-05-02DOI: 10.1538/expanim.26-0015
Cong Shi, Jianhua Sun, Jumin Niu
{"title":"Diacerein alleviates endometrial fibrosis in an intrauterine adhesion model via ferroptosis inhibition.","authors":"Cong Shi, Jianhua Sun, Jumin Niu","doi":"10.1538/expanim.26-0015","DOIUrl":"10.1538/expanim.26-0015","url":null,"abstract":"<p><p>Intrauterine adhesion (IUA) is a significant contributor to uterine infertility, primarily characterized by endometrial fibrosis. Although diacerein exhibits anti-inflammatory and anti-fibrotic properties, its therapeutic potential in IUA remains unclear. This study investigated the protective effects of diacerein in an IUA rat model induced by mechanical injury. Histological analysis revealed that diacerein treatment alleviated endometrial damage, and immunohistochemical staining confirmed the restoration of CK19 and CK18 expression, indicating improved epithelial integrity and regeneration. Diacerein mitigated endometrial fibrosis by inhibiting epithelial-mesenchymal transition (EMT), as evidenced by increased E-cadherin and decreased N-cadherin expression, likely via suppression of TGFβ/SMAD2 signaling. Diacerein exerted anti-inflammatory effects in IUA rats. Notably, diacerein inhibited ferroptosis by reducing lipid peroxidation, limiting Fe<sup>2+</sup> accumulation, and modulating ferroptosis-related proteins, including ACSL4, SLC7A11, GPX4, and FTH1. The protective effects of diacerein were mirrored by ferroptosis inhibitor Ferrostatin-1 treatment but reversed by ferroptosis inducer Erastin, confirming that diacerein alleviates endometrial fibrosis in IUA rats through ferroptosis suppression. Mechanistically, diacerein modulated the NRF2/HMGB1 signaling pathway, restoring NRF2 and HO1 levels while downregulating HMGB1 expression. Collectively, these findings suggest that diacerein effectively attenuates ferroptosis-mediated fibrosis in IUA, highlighting ferroptosis inhibition as a promising therapeutic strategy for IUA management.</p>","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":" ","pages":"383-396"},"PeriodicalIF":2.0,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13669696/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147835476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Experimental AnimalsPub Date : 2026-10-15Epub Date: 2026-07-04DOI: 10.1538/expanim.26-0044
Kenta Hayashi, Kana Nagasaka, Haruki Kitazume, Mao Urasaki, Hoang Trung Hieu, Shinichiro Nakamura, Takashi Kuramoto
{"title":"Topical administration of testosterone ameliorates atopic dermatitis of KFRS4 rats.","authors":"Kenta Hayashi, Kana Nagasaka, Haruki Kitazume, Mao Urasaki, Hoang Trung Hieu, Shinichiro Nakamura, Takashi Kuramoto","doi":"10.1538/expanim.26-0044","DOIUrl":"10.1538/expanim.26-0044","url":null,"abstract":"<p><p>Atopic dermatitis (AD) is a chronic inflammatory skin disorder influenced by genetic, environmental, and immunological factors, and its prevalence shows notable sex-associated differences. KFRS4 rats spontaneously develop AD-like dermatitis with higher severity in females, suggesting a role for sex hormones in disease modulation. This study investigated the contribution of gonadal hormones to dermatitis development in KFRS4 rats by examining the effects of gonadectomy and topical testosterone treatment. Ovariectomy did not alter dermatitis onset or severity in female rats, whereas orchiectomy markedly exacerbated dermatitis in males. Orchiectomized males developed severe lesions characterized by crusting and erosion, and exhibited significantly higher total skin lesion severity scores (TSLSS) compared with sham controls, indicating a protective role of testicular factors. To further evaluate testosterone's contribution, we applied testosterone ointment to ovariectomized females and orchiectomized males. Testosterone treatment significantly reduced TSLSS in both sexes and prevented lesion formation in the treated dorsal neck region. Histological analysis revealed increased sebaceous gland number and epidermal thickening in testosterone-treated skin, accompanied by robust induction of androgen receptor (AR)-positive cells within sebaceous glands and across epidermal layers. In contrast, dermatitis-affected skin lacked AR-positive cells, likely due to architectural disruption. In addition, testosterone treatment significantly increased the expression of filaggrin and decreased the expression of Th2 (Il4 and Il5) and Th17 (Il17a) cytokine genes. Together, these findings suggest that testosterone ameliorates dermatitis by enhancing skin barrier function and modulating type 2 and Th17 immune responses. These findings identify testosterone as a key regulator of dermatitis in KFRS4 rats and highlight androgen-mediated barrier enhancement as a potential therapeutic strategy for AD.</p>","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":" ","pages":"474-484"},"PeriodicalIF":2.0,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13669688/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148389986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}