Temporal Profile of the Renal Transcriptome of HIV-1 Transgenic Mice during Disease Progression

Abstract

Profiling of temporal changes of gene expression in the same kidney over the course of renal disease progression is challenging because repeat renal biopsies are rarely indicated in clinical practice. Here, we profiled the temporal change in renal transcriptome of HIV-1 transgenic mice (Tg26), an animal model for human HIV-associated nephropathy (HIVAN), and their littermates at three different time points (4, 8, and 12 weeks of age) representing early, middle, and late stages of renal disease by serial kidney biopsy. We analyzed both static levels of gene expression at three stages of disease and dynamic changes in gene expression between different stages. Analysis of static and dynamic changes in gene expression revealed that up-regulated genes at the early and middle stages are mostly involved in immune response and inflammation, whereas down-regulated genes mostly related to fatty acid and retinoid metabolisms. We validated the expression of a selected panel of genes that are up-regulated at the early stage (CCL2, CCL5, CXCL11, Ubd, Anxa1, and Spon1) by real-time PCR. Among these up-regulated genes, Spon1, which is a previously identified candidate gene for hypertension, was found to be up-regulated in kidney of human with diabetic nephropathy. Immunostaining of human biopsy samples demonstrated that protein expression of Spon1 was also markedly increased in kidneys of patients with both early and late HIVAN and diabetic nephropathy. Our studies suggest that analysis of both static and dynamic changes of gene expression profiles in disease progression avails another layer of information that could be utilized to gain a more comprehensive understanding of disease progression and identify potential biomarkers and drug targets.

Microarray profiling of long non-coding RNAs associated with idiopathic pulmonary arterial hypertension

“…Discrepancies between the mRNA expression profiles of the current study and previous studies are likely due to a number of limitations. For example, the IPAH RNA and protein profiles fluctuate markedly during disease progression ( 31 , 32 ), leading to variable RNA profiles. In addition, different detection platforms may have substantial impact on the profiling results and thus, subsequent experimental verification is necessary.…”

Comparison of Glomerular Transcriptome Profiles of Adult-Onset Steroid Sensitive Focal Segmental Glomerulosclerosis and Minimal Change Disease

“…Subsequently, specimens were washed three times with PBS and incubated in a 1:1000-diluted secondary antibody (goat anti mouse IgG, Thermo, Grand Island, NY) for 2 hours at room temperature. Positive staining was revealed using peroxidase-labeled streptavidin and a diaminobenzidine substrate[ 16 ]. For determination of immunohistochemistry staining, stained sections were imaged using the Image Analysis System (AxioVision 4, Carl Zeiss, Germany).…”

UBD modifies APOL1 -induced kidney disease risk

“…Like APOL1, UBD is up-regulated in response to proinflammatory stimuli including IFN-γ (8). In a mouse model of HIV-associated nephropathy, UBD is among the most up-regulated genes in the kidney (9). Previous studies have shown that intrarenal…”