Dataset Information

Transcriptional profiling of PRKG2-null growth plate identifies putative down-stream targets of PRKG2.

ABSTRACT:

Background

Kinase activity of cGMP-dependent, type II, protein kinase (PRKG2) is required for the proliferative to hypertrophic transition of growth plate chondrocytes during endochondral ossification. Loss of PRKG2 function in rodent and bovine models results in dwarfism. The objective of this study was to identify pathways regulated or impacted by PRKG2 loss of function that may be responsible for disproportionate dwarfism at the molecular level.

Methods

Microarray technology was used to compare growth plate cartilage gene expression in dwarf versus unaffected Angus cattle to identify putative downstream targets of PRGK2.

Results

Pathway enrichment of 1284 transcripts (nominal p < 0.05) was used to identify candidate pathways consistent with the molecular phenotype of disproportionate dwarfism. Analysis with the DAVID pathway suite identified differentially expressed genes that clustered in the MHC, cytochrome B, WNT, and Muc1 pathways. A second analysis with pathway studio software identified differentially expressed genes in a host of pathways (e.g. CREB1, P21, CTNNB1, EGFR, EP300, JUN, P53, RHOA, and SRC). As a proof of concept, we validated the differential expression of five genes regulated by P53, including CEBPA, BRCA1, BUB1, CD58, and VDR by real-time PCR (p < 0.05).

Conclusions

Known and novel targets of PRKG2 were identified as enriched pathways in this study. This study indicates that loss of PRKG2 function results in differential expression of P53 regulated genes as well as additional pathways consistent with increased proliferation and apoptosis in the growth plate due to achondroplastic dwarfism.

SUBMITTER: Koltes JE

PROVIDER: S-EPMC4419418 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature

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Publications

Transcriptional profiling of PRKG2-null growth plate identifies putative down-stream targets of PRKG2.

Koltes James E JE Kumar Dinesh D Kataria Ranjit S RS Cooper Vickie V Reecy James M JM

BMC research notes 20150430

<h4>Background</h4>Kinase activity of cGMP-dependent, type II, protein kinase (PRKG2) is required for the proliferative to hypertrophic transition of growth plate chondrocytes during endochondral ossification. Loss of PRKG2 function in rodent and bovine models results in dwarfism. The objective of this study was to identify pathways regulated or impacted by PRKG2 loss of function that may be responsible for disproportionate dwarfism at the molecular level.<h4>Methods</h4>Microarray technology wa ...[more]

PMID: 25924610

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Dataset Information

Transcriptional profiling of PRKG2-null growth plate identifies putative down-stream targets of PRKG2.

Background

Methods

Results

Conclusions

Publications

Transcriptional profiling of PRKG2-null growth plate identifies putative down-stream targets of PRKG2.

Similar Datasets

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