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