Dataset Information

Substrate-specific gene expression profiles in different kidney cell types are associated with Fabry disease.

ABSTRACT: Fabry disease is an X-linked lysosomal storage disorder caused by mutations in the gene encoding the ?-galactosidase A (?-Gal A) lysosomal enzyme, which results in globotriaosylceramide (Gb3) storage in vascular endothelial cells and different cell types throughout the body. Involvement of the kidney and heart is life threatening, and fibrosis of these organs is considered to be involved in the pathogenesis of Fabry disease. An increased concentration of deacylated Gb3 (lyso?Gb3) in the plasma of symptomatic patients has also been suggested as a causative molecular event. To elucidate the molecular mechanisms involved in renal fibrosis in Fabry disease, the present analyzed the changes in global gene expression prior to and following Gb3 or lyso?Gb3 treatment in two types of kidney cell lines, human proximal renal tubular epithelial (HK?2) and mouse renal glomerular mesangial (SV40 MES 13) cells. Gb3 and lyso?Gb3 treatment regulated the expression of 199 and 328 genes in each cell type, demonstrating a >2.0?fold change. The majority of the biological functions of the regulated genes were associated with fibrogenesis or epithelial?mesenchymal transition (EMT). The gene expression patterns of sphingolipid?treated HK?2 cells were distinguishable from the patterns in the SV40 MES 13 cells. Several genes associated with the EMT were selected and evaluated further in kidney cells and in Fabry mouse kidney tissues. In the SV40 MES 13 cells, the DLL1, F8, and HOXA11 genes were downregulated, and FOXP2 was upregulated by treatment with Gb3 or lyso?Gb3. In the HK?2 cells, the ADAMTS6, BEST1, IL4, and MYH11 genes were upregulated. Upregulation of the FOXP2, COL15A1, IL4, and MYH11 genes was also observed in the Fabry mouse kidney tissues. The gene expression profiles in kidney cells following the addition of Gb3 or lyso?Gb3 revealed substrate?specific and cell?specific patterns. These findings suggested that Gb3 and lyso?Gb3 lead to renal fibrosis in Fabry disease through different biochemical modulations.

SUBMITTER: Shin YJ

PROVIDER: S-EPMC4581816 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Substrate-specific gene expression profiles in different kidney cell types are associated with Fabry disease.

Shin Youn-Jeong YJ Jeon Yeo Jin YJ Jung Namhee N Park Joo-Won JW Park Hae-Young HY Jung Sung-Chul SC

Molecular medicine reports 20150701 4

Fabry disease is an X-linked lysosomal storage disorder caused by mutations in the gene encoding the α-galactosidase A (α-Gal A) lysosomal enzyme, which results in globotriaosylceramide (Gb3) storage in vascular endothelial cells and different cell types throughout the body. Involvement of the kidney and heart is life threatening, and fibrosis of these organs is considered to be involved in the pathogenesis of Fabry disease. An increased concentration of deacylated Gb3 (lyso‑Gb3) in the plasma o ...[more]

PMID: 26135632

Similar Datasets

Project description:Breast cancer is a heterogeneous disease for which prognosis and treatment strategies are largely governed by the receptor status (estrogen, progesterone and Her2-neu) of the tumor cells. Gene expression profiling of whole breast tumors further stratifies breast cancer into several molecular subtypes which also co-segregate with the receptor status of the tumor cells. We postulated that cancer associated fibroblasts (CAFs) within the tumor stroma may exhibit subtype specific gene expression profiles and thus contribute to the biology of the disease in a subtype specific manner. Several studies have reported gene expression profile differences between CAFs and normal breast fibroblasts but in none of these studies were the results stratified based on tumor subtypes. To address whether gene expression in breast cancer associated fibroblasts varies between breast cancer subtypes, we compared the gene expression profiles of early passage primary CAFs isolated from twenty human breast cancer samples representing three main subtypes; seven ER+, seven triple negative (TNBC) and six Her2+. We observed significant expression differences between CAFs derived from Her2+ breast cancer and CAFs from TNBC and ER+ cancers, particularly in pathways associated with cytoskeleton and integrin signaling. In the case of Her2+ breast cancer, the signaling pathways found to be selectively up regulated in CAFs may contribute to the more invasive properties and unfavorable prognosis of Her2+ breast cancer. These data demonstrate that in addition to the distinct molecular profiles that characterize the neoplastic cells, CAF gene expression is also differentially regulated in distinct subtypes of breast cancer. We isolated CAFs from twenty primary breast cancer samples representing three main subtypes (ER+ (n=7), TNBC (n=7), Her2+ (n=6)) and performed gene expression profile analyses on RNA isolated from these early passage CAFs. Those samples were done in two batches with 4 samples repeated in both batches. One TNBC sample was found to be an outlier and not used in the analysis.

Project description:Introduction: DSM-5 presented a revised conceptualization of specific learning disorders (LD). Contrary to former versions, the various types of LD-i.e., mathematics disorder, reading disorder, and writing disorder-are not treated as distinct diagnostic entities but are integrated into one single LD category. In support of this new classification, it has been argued that the various types of LD overlap to a great extent in their cognitive functioning profiles and therefore do not exhibit a distinct set of cognitive causes. In contrast, ICD-11 still adheres to the idea of discrete categories and thus follows the specificity hypothesis of LD. Using latent profile analysis (LPA), we therefore tested the specificity of cognitive strengths and weaknesses in children with different types of LD. Secondly, we aimed at examining the extent to which observed LD characteristics (type and severity of LD as well as IQ-achievement discrepancy) were consistent with the membership of a given latent profile. Method: 302 German third-graders (134 girls; IQ ≥ 85; M age = 111.05 months; SD = 5.76) with single or comorbid types of LD in the domains of mathematics, reading, and spelling completed a wide range of domain-specific and domain-general cognitive functioning measures. Results: Five qualitative distinct profiles of cognitive strengths and weaknesses were identified. Profile 1 (23% of the sample) showed Comprehensive Cognitive Deficits, performing low in all measures except for naming speed, language, and inhibition. Profile 2 (21%) included children with a Double Deficit in Phonological Awareness and Phonological Short-term Memory. Profile 3 (20%) was characterized by a Double Deficit of Phonological Awareness and Naming Speed. Profile 4 (19%) included children with a Single Deficit in Attention, and profile 5 (17%) consisted of children without any cognitive deficits. Moreover, type and severity of LD as well as IQ-achievement discrepancy discriminated between the profiles, which is in line with the specificity hypothesis of LD. Discussion: Overall, the finding of specific associations between the LD types and the identified cognitive profiles supports the ICD-11 classification of LD. Yet, those inferences may not be valid for an individual child but need to be examined through comprehensive diagnostic.

Dataset Information

Substrate-specific gene expression profiles in different kidney cell types are associated with Fabry disease.

Publications

Substrate-specific gene expression profiles in different kidney cell types are associated with Fabry disease.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets