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Renal Artery Stenosis Alters Gene Expression in Swine Scattered Tubular-Like Cells.

ABSTRACT: BACKGROUND:Scattered tubular-like cells (STCs) proliferate and differentiate to support neighboring injured renal tubular cells during recovery from insults. Renal artery stenosis (RAS) induces renal ischemia and hypertension and leads to loss of kidney function, but whether RAS alters renal endogenous repair mechanisms, such as STCs, remains unknown. We hypothesize that RAS in swine modifies the messenger RNA (mRNA) profile of STCs, blunting their in vitro reparative capacity. METHODS:CD24+/CD133+ STCs were isolated from pig kidneys after 10-weeks of RAS or sham (n = 3 each) and their gene cargo analyzed using high-throughput mRNAseq. Expression profiles for upregulated and downregulated mRNAs in RAS-STCs were functionally interpreted by gene ontology analysis. STC activation was assessed by counting the total number of STCs in pig kidney sections using flow cytometry, whereas cell proliferation was assessed in vitro. RESULTS:Of all expressed genes, 1430 genes were upregulated and 315 downregulated in RAS- versus Normal-STCs. Expression of selected candidate genes followed the same fold change directions as the mRNAseq findings. Genes upregulated in RAS-STCs were involved in cell adhesion, extracellular matrix remodeling, and kidney development, whereas those downregulated in RAS-STCs are related to cell cycle and cytoskeleton. The percentage of STCs from dissociated kidney cells was higher in RAS versus Normal pigs, but their proliferation rate was blunted. CONCLUSIONS:Renal ischemia and hypertension in swine induce changes in the mRNA profile of STCs, associated with increased STC activation and impaired proliferation. These observations suggest that RAS may alter the reparative capacity of STCs.

SUBMITTER: Aghajani Nargesi A

PROVIDER: S-EPMC6829501 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Renal Artery Stenosis Alters Gene Expression in Swine Scattered Tubular-Like Cells.

Aghajani Nargesi Arash A Zhu Xiang-Yang XY Liu Yuanhang Y Tang Hui H Jordan Kyra L KL Lerman Lilach O LO Eirin Alfonso A

International journal of molecular sciences 20191012 20

<h4>Background</h4>Scattered tubular-like cells (STCs) proliferate and differentiate to support neighboring injured renal tubular cells during recovery from insults. Renal artery stenosis (RAS) induces renal ischemia and hypertension and leads to loss of kidney function, but whether RAS alters renal endogenous repair mechanisms, such as STCs, remains unknown. We hypothesize that RAS in swine modifies the messenger RNA (mRNA) profile of STCs, blunting their in vitro reparative capacity.<h4>Method ...[more]

PMID: 31614781

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Project description:OBJECTIVES:Renal fibrosis is a useful biomarker for diagnosis and evaluation of therapeutic interventions of renal diseases but often requires invasive testing. Magnetization transfer magnetic resonance imaging (MT-MRI), which evaluates the presence of macromolecules, offers a noninvasive tool to probe renal fibrosis in murine renal artery stenosis (RAS) at 16.4 T. In this study, we aimed to identify appropriate imaging parameters for collagen detection at 3.0 T MRI and to test the utility of MT-MRI in measuring renal fibrosis in a swine model of atherosclerotic RAS (ARAS). MATERIALS AND METHODS:To select the appropriate offset frequency, an MT-MRI study was performed on a phantom containing 0% to 40% collagen I and III with offset frequencies from -1600 to +1600 Hz and other MT parameters empirically set as pulse width at 16 milliseconds and flip angle at 800 degrees. Then selected MT parameters were used in vivo on pigs 12 weeks after sham (n = 8) or RAS (n = 10) surgeries. The ARAS pigs were fed with high-cholesterol diet to induce atherosclerosis. The MT ratio (MTR) was compared with ex vivo renal fibrosis measured using Sirius-red staining. RESULTS:Offset frequencies at 600 and 1000 Hz were selected for collagen detection without direct saturation of free water signal, and subsequently applied in vivo. The ARAS kidneys showed mild cortical and medullary fibrosis by Sirius-red staining. The cortical and medullary MTRs at 600 and 1000 Hz were both increased. Renal fibrosis measured ex vivo showed good linear correlations with MTR at 600 (cortex: Pearson correlation coefficient r = 0.87, P < 0.001; medulla: r = 0.70, P = 0.001) and 1000 Hz (cortex: r = 0.75, P < 0.001; medulla: r = 0.83, P < 0.001). CONCLUSIONS:Magnetization transfer magnetic resonance imaging can noninvasively detect renal fibrosis in the stenotic swine kidney at 3.0 T. Therefore, MT-MRI may potentially be clinically applicable and useful for detection and monitoring of renal pathology in subjects with RAS.

Dataset Information

Renal Artery Stenosis Alters Gene Expression in Swine Scattered Tubular-Like Cells.

Publications

Renal Artery Stenosis Alters Gene Expression in Swine Scattered Tubular-Like Cells.

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