RESUMEN
The histomorphological features of normal kidneys in cats and dogs have been revealed despite the high susceptibility of cats to tubulointerstitial damage. Herein, the histological characteristics of the two species were compared. Cytoplasmic lipid droplets (LDs) were abundant in the proximal convoluted tubules (PCTs) of cats aged 23-27 months but scarce in dogs aged 24-27 months. LDs were rarely observed in the distal tubules (DTs) and collecting ducts (CDs) of either species, as visualized by the expression of Tamm-Horsfall protein 1, calbindin-D28K, and aquaporin 2. The occupational area ratio of proximal tubules (PTs) in the renal cortex was higher, but that of DTs or CDs was significantly lower in adult cats than in dogs. Single PT epithelial cells were larger, but PCT, DT, and CD lumens were significantly narrower in adult cats than in dogs. Unlike adults, young cats at 6 months exhibited significantly abundant cytoplasmic LDs in proximal straight tubules, indicating lipid metabolism-related development. Histochemistry of the 21 lectins also revealed variations in glycosylation across different renal tubules and CDs in both species. Sodium-glucose cotransporter 2 was expressed only in PTs, excluding the proximal straight tubules with few LDs in adult cats or the PCTs of young cats and adult dogs. These findings are crucial for understanding species-specific characteristics of renal histomorphology and pathogenesis.
Asunto(s)
Túbulos Renales Colectores , Especificidad de la Especie , Animales , Perros , Gatos , Túbulos Renales Colectores/metabolismo , Túbulos Renales Colectores/patología , Túbulos Renales/metabolismo , Túbulos Renales/patología , Masculino , Femenino , Gotas Lipídicas/metabolismoRESUMEN
Gestational diabetes mellitus (GDM) in human patients disrupts glucose metabolism post-pregnancy, affecting fetal development. Although obesity and genetic factors increase GDM risk, a lack of suitable models impedes a comprehensive understanding of its pathology. To address this, we administered streptozotocin (STZ, 75 mg/kg) to C57BL/6N mice for two days before pregnancy, establishing a convenient GDM model. Pregnant mice exposed to STZ (STZ-pregnant) were compared with STZ-injected virgin mice (STZ-virgin), citrate buffer-injected virgin mice (CB-virgin), and pregnant mice injected with citrate buffer (CB-pregnant). STZ-pregnant non-obese mice exhibited elevated blood glucose levels on gestational day 15.5 and impaired glucose tolerance. They also showed fewer normal fetuses compared to CB-pregnant mice. Additionally, STZ-pregnant mice had the highest plasma C-peptide levels, with decreased pancreatic islets or increased alpha cells compared to CB-pregnant mice. Kidneys isolated from STZ-pregnant mice did not display histological alterations or changes in gene expression for the principal glucose transporters (GLUT2 and SGLT2) and renal injury-associated markers. Notably, STZ-pregnant mice displayed decreased gene expression of insulin-receiving molecules (ISNR and IGFR1), indicating heightened insulin resistance. Liver histology in STZ-pregnant mice remained unchanged except for a pregnancy-related increase in lipid droplets within hepatocytes. Furthermore, the duodenum of STZ-pregnant mice exhibited increased gene expression of ligand-degradable IGFR2 and decreased expression of GLUT5 and GLUT12 (fructose and glucose transporters, respectively) compared to STZ-virgin mice. Thus, STZ-pregnant mice displayed GDM-like symptoms, including fetal abnormalities, while organs adapted to impaired glucose metabolism by altering glucose transport and insulin reception without histopathological changes. STZ-pregnant mice offer a novel model for studying mild onset non-obese GDM and species-specific differences in GDM features between humans and animals.
Asunto(s)
Diabetes Mellitus Experimental , Diabetes Gestacional , Femenino , Embarazo , Ratones , Humanos , Animales , Estreptozocina/toxicidad , Ratones Endogámicos C57BL , Insulina/metabolismo , Diabetes Mellitus Experimental/metabolismo , Obesidad , Glucosa/metabolismo , Fenotipo , Citratos , Glucemia/metabolismoRESUMEN
This paper demonstrates an optical technique to measure magnetostrictive strain in a cryogenic environment using a Fabry-Pérot resonator spaced by crystal samples. Optical measurement techniques are calibration-free and highly sensitive. This technique was used to measure the magnetostrictive strain of neodymium gallate at a temperature of 49 mK to be λ = 1.3 × 10-5 at 3 T, with a sensitivity of 3.0 × 10-8. We highlight the interesting properties of the crystal's magnetic ordering. The sensitivity of this technique was limited by the wavemeter used to measure the laser frequency, and significant improvements in the sensitivity should be possible.
RESUMEN
Background: Interleukin (IL)-17-producing γδT (γδT17) cells mediate inflammatory responses in barrier tissues. Dysregulated γδT17 cell activation can lead to the overproduction of IL-17 and IL-22 and the development of inflammatory diseases, including psoriasis. IL-23 and IL-1ß are known to synergistically activate γδT17 cells, but the regulatory mechanisms of γδT17 cells have not been fully elucidated. This study aimed to reveal the contribution of the inflammatory cytokine tumor necrosis factor-like ligand 1A (TL1A) to γδT17 cell activation and psoriasis development. Methods: Anti-TL1A antibody was injected into an imiquimod (IMQ)-induced murine psoriasis model. TL1A receptor expression was analyzed in splenic and dermal γδT cells. γδT cells were tested for cytokine production in vitro and in vivo under stimulation with IL-23, IL-1ß, and TL1A. TL1A was applied to a psoriasis model induced by intradermal IL-23 injection. Mice deficient in γδT cells were intradermally injected with IL-23 plus TL1A to verify the contribution of TL1A-dependent γδT-cell activation to psoriasis development. Results: Neutralization of TL1A attenuated γδT17 cell activation in IMQ-treated skin. TL1A induced cytokine production by splenic γδT17 cells in synergy with IL-23. Dermal γδT17 cells constitutively expressed a TL1A receptor at high levels and vigorously produced IL-22 upon intradermal IL-23 and TL1A injection but not IL-23 alone. TL1A exacerbated the dermal symptoms induced by IL-23 injection in wild-type but not in γδT cell-deficient mice. Conclusion: These findings suggest a novel regulatory mechanism of γδT cells through TL1A and its involvement in psoriasis pathogenesis as a possible therapeutic target.
Asunto(s)
Psoriasis , Animales , Ratones , Citocinas/metabolismo , Imiquimod/uso terapéutico , Interleucina-23 , Ligandos , Psoriasis/patologíaRESUMEN
Systemic autoimmune diseases (ADs) might affect the morphology and function of gut-associated lymphoid tissue (LTs) indirectly; however, their exact relationship remains unclear. Therefore, we investigated mouse LTs in the anorectal canal and morphologically compared them between MRL/MpJ-Fas+/+ and MRL/MpJ-Faslpr/lpr mice. LT aggregations, also known as rectal mucosa-associated lymphoid tissues (RMALTs), were exclusively seen in the lamina propria and submucosa of the rectum. The mean size and number of the LT aggregations both significantly increased in MRL/MpJ-Faslpr/lpr mice compared to those in MRL/MpJ-Fas+/+ mice. The distance from the anorectal junction to the first LT aggregate was significantly shorter in MRL/MpJ-Faslpr/lpr mice than that in MRL/MpJ-Fas+/+ mice. Immunostaining revealed that the RMALTs included CD3+, CD4+, and CD8+ T cells; B220+ B cells; IBA1+ macrophages; Ki67+ proliferative cells; and PNAd+ high-endothelial venules (HEVs). The numbers of macrophages, proliferative cells, CD4+ T cells, CD8+ T cells, and HEVs were significantly increased in MRL/MpJ-Faslpr/lpr mice compared to those in MRL/MpJ mice. Furthermore, the gene expression levels of chemokines (Cxcl9 and Cxcl13) and their corresponding receptors (Cxcr3 and Cxcr5) were significantly higher in MRL/MpJ-Faslpr/lpr mice than those in MRL/MpJ-Fas+/+ mice. Although the morphology of rectal epithelium was comparable between the strains, M cell number was significantly higher in MRL/MpJ-Faslpr/lpr mice than in MRL/MpJ-Fas+/+ mice. Thus, ADs could alter RMALT morphology, and quantitative changes in T-cell subsets, proliferative cells, macrophages, HEVs, chemokine expression, and M cells could affect their cell composition and development.