Dataset Information

Mouse kidney glomerular extracellular matrix LC-MSMS

ABSTRACT: Across the spectrum of human disease there are significant changes in the composition and organisation of extracellular matrix (ECM). Furthermore, disease severity can vary according to race and sex, yet mechanisms for these variations are unclear. Using the kidney glomerulus as a model system, we tested the hypothesis that genetic background and sex influence composition and organisation of ECM. We characterised ECM from healthy mice with different predisposition to glomerular disease using global microarray, discovery proteomics and electron microscopy. Transcriptomic and proteomic analyses revealed unique strain and sex dependent glomerular ECM signatures with novel ECM proteins, which relate to glomerular dysfunction with leakage of macromolecules into the glomerular filtrate. In addition, we found striking structural changes in basement membranes in disease-susceptible mice. These findings were not explained by mutations in known ECM or glomerular genes. Pathway analysis of merged transcriptomic and proteomic datasets identified potential ECM regulatory pathways involving inhibition of matrix metalloproteinases, LXR/RXR, NRF2, notch and CDK5. These pathways may therefore alter ECM and confer susceptibility to disease.

INSTRUMENT(S): LTQ Orbitrap Elite

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Kidney

SUBMITTER: M Randles

LAB HEAD: Rachel Lennon

PROVIDER: PXD000811 | Pride | 2016-07-09

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	20121123_1in10_MRA1.DAT-pride.pride.mgf.gz	Mgf
	20121123_1in10_MRA1.DAT-pride.pride.mztab.gz	Mztab
	20121123_1in10_MRA1.DAT-pride.xml.gz	Xml
	20121123_1in10_MRA1.raw	Raw
	20121123_1in10_MRA10.DAT-pride.pride.mgf.gz	Mgf

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Publications

Genetic Background is a Key Determinant of Glomerular Extracellular Matrix Composition and Organization.

Randles Michael J MJ Woolf Adrian S AS Huang Jennifer L JL Byron Adam A Humphries Jonathan D JD Price Karen L KL Kolatsi-Joannou Maria M Collinson Sophie S Denny Thomas T Knight David D Mironov Aleksandr A Starborg Toby T Korstanje Ron R Humphries Martin J MJ Long David A DA Lennon Rachel R

Journal of the American Society of Nephrology : JASN 20150420 12

Glomerular disease often features altered histologic patterns of extracellular matrix (ECM). Despite this, the potential complexities of the glomerular ECM in both health and disease are poorly understood. To explore whether genetic background and sex determine glomerular ECM composition, we investigated two mouse strains, FVB and B6, using RNA microarrays of isolated glomeruli combined with proteomic glomerular ECM analyses. These studies, undertaken in healthy young adult animals, revealed uni ...[more]

PMID: 25896609

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