In vitro studies identified TBC1D4 as an regulator of renal ion and water transporting proteins. However, TBC1D4-deficient mice did not show a defective renal salt and water homeostasis.
Rab-GAP TBC1D4 (AS160) is dispensable for the renal control of sodium and water homeostasis but regulates GLUT4 in mouse kidney.
Sex, Specimen part
View SamplesThe endocytic receptor megalin constitutes the main pathway for clearance of plasma proteins from the glomerular filtrate in the proximal tubules. However, little is know about the mechanisms that control receptor activity. A widely discussed hypothesis states that the intracellular domain (ICD) of megalin, released upon ligand binding, acts as a transcription regulator to suppress receptor expression - a mechanism proposed to safeguard the proximal tubules from protein overload. Here, we have put this hypothesis to the test by generating a mouse model co-expressing the soluble ICD and the full-length receptor. Despite pronounced expression in the proximal tubules, the ICD failed to exert any effects on renal proximal tubular function such as megalin expression, protein retrieval, or renal gene transcription. Thus, our data argue that the ICD does not play a role in regulation of megalin activity in vivo in the proximal tubules.
The soluble intracellular domain of megalin does not affect renal proximal tubular function in vivo.
Sex, Age, Specimen part
View SamplesExpression data from Breast cancer subtypes
Chronic oxidative stress promotes H2AX protein degradation and enhances chemosensitivity in breast cancer patients.
Disease, Cell line
View SamplesIn a cohort study of 7 women with primary invasive breast cancer, we obtained a tumor specimen before (biopsy) and after (tumorectomy) 4 cycles of NAC with epirubicine and cyclophosphamide, followed by 4 cycles of taxanes. Total RNA was extracted from tumor specimens and the whole transcriptome was quantified with Affymetrix HuGene1.1ST. Molecular functions changing during chemotherapy were searched.
Chronic oxidative stress promotes H2AX protein degradation and enhances chemosensitivity in breast cancer patients.
Specimen part, Subject, Time
View Samples10 biopsies before treatment from triple negative patients with complete response were collected. Total RNA was extracted from tumor specimens and the whole transcriptome was quantified with Affymetrix HuGene1.1ST. The biopsies were classified into Good (major or complete) or Poor (absent or minor) therapeutic response subgroup.
Chronic oxidative stress promotes H2AX protein degradation and enhances chemosensitivity in breast cancer patients.
Sex, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Impaired neutrophil function in 24p3 null mice contributes to enhanced susceptibility to bacterial infections.
Sex, Age, Specimen part
View SamplesLipocalin 24p3 (24p3) is a neutrophil secondary granule protein. 24p3 is also a siderocalin, which binds several bacterial siderophores. It was therefore proposed that synthesis and secretion of 24p3 by stimulated macrophages or release of 24p3 upon neutrophil degranulation sequesters iron-laden siderophores to attenuate bacterial growth. Accordingly, 24p3-deficient mice are susceptible to bacterial pathogens whose siderophores would normally be chelated by 24p3. Specific granule deficiency (SGD) is a rare congenital disorder characterized by complete absence of proteins in secondary granules. Neutrophils from SGD patients, who are prone to bacterial infections, lack normal functions but the potential role of 24p3 in neutrophil dysfunction in SGD is not known. Here we show that neutrophils from 24p3-deficient mice are defective in many neutrophil functions. Specifically, neutrophils in 24p3-deficient mice do not extravasate to sites of infection and are defective for chemotaxis. A transcriptome analysis revealed that genes that control cytoskeletal reorganization are selectively suppressed in 24p3-deficient neutrophils. Additionally, small regulatory RNAs (miRNAs) that control upstream regulators of cytoskeletal proteins are also increased in 24p3-deficient neutrophils. Further, 24p3-deficient neutrophils failed to phagocytose bacteria, which may account for the enhanced sensitivity of 24p3-deficient mice to both intracellular (Listeria monocytogenes) and extracellular (Candida albicans, Staphylococcus aureus) pathogens. Interestingly, Listeria does not secrete siderophores and additionally, the siderophore secreted by Candida is not sequestered by 24p3. Therefore, the heightened sensitivity of 24p3-deficient mice to these pathogens is not due to sequestration of siderophores limiting iron availability, but is a consequence of impaired neutrophil function.
Impaired neutrophil function in 24p3 null mice contributes to enhanced susceptibility to bacterial infections.
Sex, Age, Specimen part
View SamplesMicroarray analysis was performed to identify transcriptional changes that occur during mucociliary differentiation of human primary bronchial epithelial cells cultured at an air-liquid interface (ALI).
Transcriptional profiling of mucociliary differentiation in human airway epithelial cells.
No sample metadata fields
View SamplesPuberty unmasks or accelerates nephropathies, including the nephropathy of diabetes mellitus (DM). A number of cellular systems implicated in the kidney disease of DM interweave, forming an interdependent functional web. We performed focused microarray analysis to test the hypothesis that one or more genes in the transforming growth factor beta (TGF-) signaling system would be differentially regulated in male rats depending on the age of onset of DM.
Prepubertal onset of diabetes prevents expression of renal cortical connective tissue growth factor.
No sample metadata fields
View SamplesGenetic comparison between periosteal skeletal stem cells and bone marrow skeletal stem cells in mice
Comparative analysis of gene expression identifies distinct molecular signatures of bone marrow- and periosteal-skeletal stem/progenitor cells.
Specimen part
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