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Series GSE87212 Query DataSets for GSE87212
Status Public on Aug 31, 2017
Title Targeting Phospholipase D4 attenuates kidney fibrosis by modulating immune system and activating proteases
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Phospholipase D4 (PLD4), a single pass transmembrane glycoprotein, is amongst the most highly upregulated genes in mice kidneys subjected to chronic progressive fibrosis1. Here we characterized the expression pattern of PLD4 and found it to be over expressed in the proximal and distal tubular epithelial cells of mice and human kidneys following fibrosis. Subcellularly, PLD4 was localized to the endoplasmic reticulum, golgi apparatus and mitochondria and was confirmed to interact with Calmegin, Lectin, Mannose Binding 2 and Suppressor of Lin-12-Like Protein 1. Mechanistically, we show that PLD4 facilitates fibrogenesis by modulating innate and adaptive immune system thereby promoting TGF-β signaling pathway. Moreover, PLD4 induces the expression of α1-antitrypsin protein (AAT, a serine protease inhibitor) that results in subsequent down-regulation of Neutrophil Elastase (NE), thereby leading to the accumulation of extracellular proteins and scar tissue formation. Genetic silencing of PLD4 protected mice from development of fibrosis initiated by either Folic acid (FA) treatment or unilateral ureteral obstruction (UUO). Furthermore, therapeutic targeting of PLD4 using specific siRNA also protected the mice from kidney fibrosis via the same mechanisms. These results suggest that inhibition of PLD4 is sufficient to activate protease-mediated degradation of extracellular matrix and reversal of fibrosis thereby highlighting new therapeutic strategies.
Overall design mRNA profiles in the kidneys of PLD4-/- and PLD4+/+ mice at baseline and following UUO at days 5 and 10 with 4 replicates using Illumina NextSeq500
Contributor(s) Vaidya V, Herbert Z
Citation(s) 28814511
Submission date Sep 22, 2016
Last update date May 15, 2019
Contact name Zach Herbert
Organization name Dana-Farber Cancer Institute
Department Molecular Biology Core Facilities
Street address 450 Brookline Ave
City Boston
State/province MA
ZIP/Postal code 02215
Country USA
Platforms (1)
GPL19057 Illumina NextSeq 500 (Mus musculus)
Samples (24)
GSM2325602 WT_N_1
GSM2325603 WT_N_2
GSM2325604 WT_N_3
BioProject PRJNA343890
SRA SRP090295

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Supplementary file Size Download File type/resource
GSE87212_Normalized_FPKM_Gene_Counts.csv.gz 1.7 Mb (ftp)(http) CSV
GSE87212_Raw_Gene_Counts.csv.gz 796.9 Kb (ftp)(http) CSV
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