{"title":"Morphological analysis of autophagy in axonal degeneration in gracile axonal dystrophy mice.","authors":"Yusuke Tokuhara, Shinichiro Ukon, Shohei Watanabe, Yoshiki Tatsumi, Hiroo Yoshikawa, Masaki Ohmuraya, Takashi Kimura","doi":"10.1538/expanim.24-0041","DOIUrl":"https://doi.org/10.1538/expanim.24-0041","url":null,"abstract":"<p><p>Gracile axonal dystrophy (gad) mutant mice present with autosomal recessive inherited sensory ataxia in the early stages, followed by age-dependent motor ataxia. This phenotype is caused by a mutation in the ubiquitin carboxyl-terminal hydrolase isozyme L1 (UCH-L1) gene and leads to a lack of expression of UCH-L1 protein, which is related with the autophagy pathway and the ubiquitin-proteasome system (UPS). To elucidate the pathophysiology of abnormal protein accumulation in gad mice, we focused on macroautophagy. Using electron microscopy, we detected a double-membrane structure, which was characteristic of autophagosomes, in gad mice. In addition, on immunohistochemistry to investigate the expression levels of autophagy-related proteins in the gracile nuclei of the gad mouse, we found upregulation of LC3 and p62 but not LAMP-2A. These results suggested that a lack of UCH-L1 expression might induce the formation of autophagosomes, but the resulting autophagy flux might be disturbed.</p>","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142617015","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}
{"title":"Transcriptomics and metabolomics analysis of the pathogenesis of a novel hyperlipidemia-susceptible rat strain.","authors":"Xiufeng Ai, Qian Zhang, Quanxin Ma, Mingsun Fang, Keyan Zhu, Yueqin Cai, Qinqin Yang, Lizong Zhang","doi":"10.1538/expanim.24-0080","DOIUrl":"https://doi.org/10.1538/expanim.24-0080","url":null,"abstract":"<p><p>To investigate the pathogenesis of hyperlipidemia in Wistar-SD Hypercholesterolemia (WSHc) rats and clarify the genetic and biological characteristics. Six 7-8-week-old WSHc rats were fed a high-fat diet (HFD), and another six were fed ordinary feed, with age-matched Wistar rats as the control group under the same treatment. After 16 weeks, serum lipid levels were measured. A transcriptomic analysis of the differences in gene expression of the liver related to cholesterol metabolism was conducted, and 119 differentially expressed genes were discovered through bioinformatics analysis and molecular biology verification. UHPLC-Q-TOF/MS was applied for lipidomic analysis of serum samples from each group. WSHc rats developed dyslipidemia after a high-fat diet was induced. Investigation of the gene profiles using the protein-protein interaction network and one-cluster clustering analysis identified SREBF1 as a HUB gene and NR1d1 as an independent key gene. SREBF1 and NR1d1 were further validated in molecular biology experiments, which was consistent with the transcriptomic results. Lipid metabolomics analysis identified seven lipid subclasses and 84 lipid molecules. The metabolic profiles of serum lipid media of the WSHc + HFD and WSHc + SC groups were significantly different compared to that of the control group by 62 and 70 lipid molecules, respectively. Differential metabolites were produced via sphingolipid and glycerophospholipid metabolism. A stable model of hypercholesterolemia in WSHc rats can be generated by feeding on a high-fat diet, and the pathogenesis mainly involves two key genes, SREBF1 and NR1d1, and the sphingolipid and glycerophospholipid metabolism pathways.</p>","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142575520","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}
Jiazhi Cao, Hao Feng, Lutong Li, Wenwu Ling, Hong Wang
{"title":"High-frequency ultrasound for assessing the renal characteristics of spontaneous type 2 diabetes mellitus db/db mice.","authors":"Jiazhi Cao, Hao Feng, Lutong Li, Wenwu Ling, Hong Wang","doi":"10.1538/expanim.24-0114","DOIUrl":"https://doi.org/10.1538/expanim.24-0114","url":null,"abstract":"<p><p>There are few ultrasonographic studies on the spontaneous T2DM db/db mouse. Our objective was to dynamically investigate and assess renal morphological and hemodynamic changes in spontaneous type 2 diabetes mellitus db/db mice through high-frequency ultrasound. Eighteen male db/db mice (the model group) and twelve male db/+ mice (the control group) were included. Body weight and fasting blood glucose were measured at the ages of 8, 16 and 32 weeks. High-frequency ultrasound examinations were conducted at the same ages. Compared with those in the control group, H&E and Masson staining revealed pathological changes in the renal tissue of the db/db mice at 16 weeks of age, and the lesions were significantly aggravated at 32 weeks of age. The body mass of the mice in the model group increased significantly at 8, 16 and 32 weeks of age, and the kidney volume measured by ultrasound also increased with age. Compared with those of the control group, the blood flow scores determined via power Doppler were significantly different. The peak systolic velocity (PSV), end diastolic velocity (EDV), and resistive index (RI) of the renal artery and the PSV, EDV, and RI of the segmental artery were significantly different at the 16th week compared with those that at the eighth week. The results of high-frequency ultrasound revealed that the renal hemodynamics of db/db mice changed at the sixteen weeks.</p>","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142497650","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 : 2024-10-23Epub Date: 2024-07-02DOI: 10.1538/expanim.23-0178
Peng Lian, Zhirong Huan, Yan Wang, Hao Yao, Shuguang Han, Xin Ge
{"title":"Protective effect of 8-Gingerol, a potent constituent of ginger, on acute lung injury following hemorrhagic shock in rats.","authors":"Peng Lian, Zhirong Huan, Yan Wang, Hao Yao, Shuguang Han, Xin Ge","doi":"10.1538/expanim.23-0178","DOIUrl":"10.1538/expanim.23-0178","url":null,"abstract":"<p><p>Acute lung injury (ALI) is a common complication after hemorrhagic shock (HS), which is associated with HS-induced inflammatory response, oxidative stress, and cell apoptosis. This study aimed to investigate the therapeutic efficacy of 8-Gingerol, a constituent extracted from ginger, on ALI after HS in rats. We established a fixed press hemorrhage model in SD rats, in which the HS rats were administered 15 or 30 mg/kg of 8-Gingerol by intraperitoneal injection before fluid resuscitation. Hematoxylin and eosin (H&E) and TUNEL staining were performed to evaluate histopathological changes and cell apoptosis in lung tissues, respectively. Quantitative reverse transcription PCR and western blot were used to measure gene and protein expression. Pro-inflammatory cytokines were detected by ELISA kits. Immunofluorescence of myeloperoxidase was used to evaluate neutrophil infiltration. 8-Gingerol reduced pulmonary edema, alveolar wall thickness, and cell apoptosis in lung tissues of HS rats. Regarding inflammatory responses, 8-Gingerol attenuated neutrophil infiltration in lung tissues, reduced pro-inflammatory cytokines in lung tissues and bronchoalveolar lavage fluid, and decreased the levels of NLR family, pyrin domain containing 3 (NLRP3), PYD and CARD domain containing (ASC), and Cleaved-Caspase 1 (Asp296), p20 (Cleaved Caspase 1) in lung tissues. Additionally, 8-Gingerol ameliorated oxidative stress in lung tissues as evidenced by increased antioxidant indicators (SOD and GSH) and decreased production of malondialdehyde (MDA) and reactive oxygen species (ROS). The therapeutic effects of 8-Gingerol were associated with the regulation of mitogen-activated protein kinase (MAPK) and Nrf2/HO-1 pathways. These results support 8-Gingerol as a promising drug for the treatment of HS-induced ALI.</p>","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":" ","pages":"446-457"},"PeriodicalIF":2.2,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11534488/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141497536","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":"Relationship between aging and periodontal disease severity in gauge-raised cynomolgus monkeys (Macaca fascicularis).","authors":"Takaharu Sone, Motohiro Komaki, Tadashi Sankai, Hiroko Hiramine, Kiyoko Watanabe, Nobushiro Hamada, Toshiro Kodama","doi":"10.1538/expanim.23-0141","DOIUrl":"10.1538/expanim.23-0141","url":null,"abstract":"<p><p>The study aimed to evaluate the periodontal disease status in different age groups and clarify the relationship between aging and the severity of periodontal disease. The test animals were cynomolgus monkeys that were born and raised at Tsukuba Primate Research Center, National Institutes of Biomedical Innovation, Health and Nutrition. The participants were divided into three groups: young (5-10 years old), middle (10-19 years old), and old (≥20 years old). The Plaque Index (PLI), Gingival Index (GI), Probing pocket depth (PPD), and Bleeding on probing (BOP) were used for the periodontal examination. Representative teeth were also examined. Polymerase chain reaction (PCR) was used to identify Porphyromonas macacae in dental plaque. Multiple comparisons and regression analyses were used to analyze the relationship between each age group and each oral examination index. Statistically significant differences were found between the age groups and periodontal examination index. Multiple regression analysis revealed that age was strongly correlated with each oral examination index. Based on these results, oral examinations of cynomolgus monkeys kept in the same environment confirmed an association between aging and periodontal disease severity. Monkeys at this facility are expected to serve as new experimental models for elucidating the mechanisms underlying the progression of age-related periodontal disease.</p>","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":" ","pages":"390-398"},"PeriodicalIF":2.2,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11534493/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141175181","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 : 2024-10-23Epub Date: 2024-06-28DOI: 10.1538/expanim.24-0021
Nurinee Dolrahman, Wachiryah Thong-Asa
{"title":"Beta-sitosterol mitigates cognitive deficit and hippocampal neurodegeneration in mice with trimethyltin-induced toxicity.","authors":"Nurinee Dolrahman, Wachiryah Thong-Asa","doi":"10.1538/expanim.24-0021","DOIUrl":"10.1538/expanim.24-0021","url":null,"abstract":"<p><p>The present study investigated the neural health benefit of beta-sitosterol (BSS) against trimethyltin (TMT)-induced neurodegeneration in mice. Forty male Institute of Cancer Research (ICR) mice were randomly divided into Sham-veh, TMT-veh, TMT-BSS50, and TMT-BSS100. A one-time intraperitoneal injection of 2.6 mg/kg of TMT was given to mice in TMT groups. Vehicle (veh), BSS 50 mg/kg or BSS 100 mg/kg were orally given for 2 weeks. Spatial learning and memory were evaluated. Brain oxidative status, hippocampal neuropathology, and reactive astrocytes were done. White matter pathology was also evaluated. The results indicated the massy effect of TMT on induced motor ability and spatial memory deficits in accordance with increased neuronal degeneration in Cornus ammonis (CA) 1, CA3, and dentate gyrus (DG) and internal capsule white matter damage. TMT also induced the reduction of reactive astrocytes in CA1 and DG. Brain's catalase activity was significantly reduced by TMT, but not in mice with BSS treatments. Both doses of BSS treatment exhibited improvement in motor ability and spatial memory deficits in accordance with the activation of reactive astrocytes in CA1, CA3, and DG. However, they successfully prevented the increase of neuronal degeneration in CA1 found only with the BSS dose of 100 mg/kg, and it was indicated as the effective dose for neuroprotection in the vulnerable brain area. This study demonstrated mitigative effects of BSS against motor ability and memory deficits with neural health benefits, including a protective effect against CA1 neurodegeneration and a nurturing effect on hippocampal reactive astrocytes.</p>","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":" ","pages":"433-445"},"PeriodicalIF":2.2,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11534485/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141467170","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 : 2024-10-23Epub Date: 2024-05-25DOI: 10.1538/expanim.24-0020
Zhi-Hui Guan, Di Yang, Yi Wang, Jia-Bin Ma, Guo-Nian Wang
{"title":"Ectodysplasin-A2 receptor (EDA2R) knockdown alleviates myocardial ischemia/reperfusion injury through inhibiting the activation of the NF-κB signaling pathway.","authors":"Zhi-Hui Guan, Di Yang, Yi Wang, Jia-Bin Ma, Guo-Nian Wang","doi":"10.1538/expanim.24-0020","DOIUrl":"10.1538/expanim.24-0020","url":null,"abstract":"<p><p>Ischemia/reperfusion (I/R) is a pathological process that occurs in numerous organs and is often associated with severe cellular damage and death. Ectodysplasin-A2 receptor (EDA2R) is a member of the TNF receptor family that has anti-inflammatory and antioxidant effects. However, to the best of our knowledge, its role in the progression of myocardial I/R injury remains unclear. The present study aimed to investigate the role of EDA2R during myocardial I/R injury and the molecular mechanisms involved. In vitro, dexmedetomidine (DEX) exhibited a protective effect on hypoxia/reoxygenation (H/R)-induced cardiomyocyte injury and downregulated EDA2R expression. Subsequently, EDA2R silencing enhanced cell viability and reduced the apoptosis of cardiomyocytes. Furthermore, knockdown of EDA2R led to an elevated mitochondrial membrane potential (MMP), repressed the release of Cytochrome C and upregulated Bcl-2 expression. EDA2R knockdown also resulted in downregulated expression of Bax, and decreased activity of Caspase-3 and Caspase-9 in cardiomyocytes, reversing the effects of H/R on mitochondria-mediated apoptosis. In addition, knockdown of EDA2R suppressed H/R-induced oxidative stress. Mechanistically, EDA2R knockdown inactivated the NF-κB signaling pathway. Additionally, downregulation of EDA2R weakened myocardial I/R injury in mice, as reflected by improved left ventricular function and reduced infarct size, as well as suppressed apoptosis and oxidative stress. Additionally, EDA2R knockdown repressed the activation of NF-κB signal in vivo. Collectively, knockdown of EDA2R exerted anti-apoptotic and antioxidant effects against I/R injury in vivo and in vitro by suppressing the NF-κB signaling pathway.</p>","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":" ","pages":"376-389"},"PeriodicalIF":2.2,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11534487/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141155015","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 : 2024-10-23Epub Date: 2024-08-03DOI: 10.1538/expanim.23-0149
Daniela Romina Montagna, María Florencia Todero, Gabriela Cintia Postma, Roberto Trigo, Alan Bernal, Oscar Bustuoabad, Mónica Vermeulen, Raúl Ruggiero, Alejandra Duarte
{"title":"Resistance against the development of diethylnitrosamine-induced hepatocellular carcinoma in female C3H mice: an experimental model.","authors":"Daniela Romina Montagna, María Florencia Todero, Gabriela Cintia Postma, Roberto Trigo, Alan Bernal, Oscar Bustuoabad, Mónica Vermeulen, Raúl Ruggiero, Alejandra Duarte","doi":"10.1538/expanim.23-0149","DOIUrl":"10.1538/expanim.23-0149","url":null,"abstract":"<p><p>Histopathological features of hepatocellular carcinoma (HCC) induced by diethylnitrosamine (DEN) in mice display strong similarities with those seen in humans, including the higher tumor prevalence in males than in females. Previous studies have demonstrated that continual production of the pro-inflammatory IL-6 by Kupffer cells is involved in the initiation and progression of DEN-induced HCC and that estrogen-mediated reduction of IL-6 secretion would decrease its incidence in females. Given the predominant utilization of male mice in hepatic carcinogenesis research, the objective of this study was to examine histopathological and immunological parameters in the DEN-induced liver carcinogenesis model in female C3H mice. We observed a significant prevalence of hepatocellular hyperplasias and adenomas alongside a minimal infiltration of inflammatory cells and a scarcity of senescent areas in females. Further, a low expression of immunosuppression markers is observed in females - such as neutrophil/lymphocyte ratio, PD-1 expression in CD8 T cells, and PD-L1 in myeloid cells - compared to males. Comparative studies between susceptible and resistant hosts to chemical carcinogenesis may help to unveil novel therapeutic strategies against cancer.</p>","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":" ","pages":"399-411"},"PeriodicalIF":2.2,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11534494/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141888882","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":"Double-decker cage reduces mount frequency and ejaculation latency, resulting in reduced weight loss in male rats after mating behavior.","authors":"Tomoki Bo, Naoki Fukuda, Junko Ozaki, Ayumi Inoue, Kiyoaki Katahira, Tsunekata Ito","doi":"10.1538/expanim.24-0026","DOIUrl":"10.1538/expanim.24-0026","url":null,"abstract":"<p><p>Rats were the first mammals to be domesticated for scientific research, and abundant physiological data are available on them. Rats are expected to continue to play an important role as experimental animals, especially with advancements such as CRISPR/Cas9 technology. Environmental enrichment aims to promote species-specific behaviors and psychological well-being. In the present study, we designed a double-decker (DD) cage, which utilizes two stacked plastic cages for rat enrichment, and investigated the influence of housing in the DD cage on rat mating behavior. The results indicated that mount frequency, total mount counts, and total ejaculation latency were significantly lower in the DD cages than in the single-decker (SD) cages. Notably, in the DD cages, the body weight loss of male rats after mating behavior was lower than that observed in the SD cage. Water consumption per day during mating behavior was also significantly lower in the DD cages, although no significant differences were observed in daily food intake during mating behavior. In addition, reproductive performance, including pregnancy rate and birth rate, did not change in the DD cages. In summary, our study demonstrated that DD cages reduce mount frequency and ejaculation latency during rat mating, resulting in decreased water consumption and weight loss in male rats. Therefore, housing in DD cages may serve as a beneficial enrichment for rats.</p>","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":" ","pages":"412-420"},"PeriodicalIF":2.2,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11534486/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141175178","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 : 2024-10-23Epub Date: 2024-06-29DOI: 10.1538/expanim.24-0043
Masanori A Murayama
{"title":"Complement C3 deficient mice show more severe imiquimod-induced psoriasiform dermatitis than wild-type mice regardless of the commensal microbiota.","authors":"Masanori A Murayama","doi":"10.1538/expanim.24-0043","DOIUrl":"10.1538/expanim.24-0043","url":null,"abstract":"<p><p>The complement active product, C3a, and the receptor C3aR comprise an axis that exerts various biological functions, such as protection against infection. C3a is highly expressed in the inflamed skin and blood from patients with psoriasiform dermatitis. However, the role of the C3a/C3aR axis in psoriasiform dermatitis remains unclear because conflicting results using C3<sup>-/-</sup> mice have been published. In this study, to elucidate the contribution of commensal microbiota in C3<sup>-/-</sup> and wild-type (WT) mice were subjected to imiquimod-induced psoriasiform dermatitis under different housing conditions. C3<sup>-/-</sup> mice showed increased epidermal thickness and keratinocyte proliferation markers in the inflamed ear compared to WT mice upon treatment with IMQ. These inflamed phenotypes were observed in both cohoused and separately housed conditions, and antibiotic treatment did not abolish the aggravation of IMQ-induced psoriasiform dermatitis in C3<sup>-/-</sup> mice. These results suggested that the difference of commensal microbiota is not important for the C3-involved psoriasiform dermatitis. Keratinocyte hyperproliferation is a major feature of the inflamed skin in patients with psoriasiform dermatitis. In vitro experiments showed that C3a and C3aR agonists inhibited keratinocyte proliferation, which was abolished by introduction of a C3aR antagonist. Collectively, these results suggest that the C3a/C3aR axis plays a critical role in psoriasiform dermatitis development by inhibiting keratinocyte proliferation, regardless of the regulation of the commensal microbiota.</p>","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":" ","pages":"458-467"},"PeriodicalIF":2.2,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11534491/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141467171","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}