TY - JOUR
T1 - Untargeted gas chromatography–mass spectrometry-based metabolomics analysis of kidney and liver tissue from the Lewis Polycystic Kidney rat
AU - Abbiss, Hayley
AU - Maker, Garth L.
AU - Gummer, Joel P. A.
AU - Rawlinson, Catherine
AU - Musk, Gabrielle C.
AU - Fleming, Patricia A.
AU - Phillips, Jacqueline K.
AU - Boyce, Mary C.
AU - Trengove, Robert D.
PY - 2019/6/15
Y1 - 2019/6/15
N2 - Polycystic kidney disease (PKD) encompasses a spectrum of inherited disorders that lead to end-stage renal disease (ESRD). There is no cure for PKD and current treatment options are limited to renal replacement therapy and transplantation. A better understanding of the pathobiology of PKD is needed for the development of new, less invasive treatments. The Lewis Polycystic Kidney (LPK) rat phenotype has been characterized and classified as a model of nephronophthisis (NPHP9, caused by mutation of the Nek8 gene) for which polycystic kidneys are one of the main pathologic features. The aim of this study was to use a GC–MS-based untargeted metabolomics approach to determine key biochemical changes in kidney and liver tissue of the LPK rat. Tissues from 16-week old LPK (n = 10) and Lewis age- and sex-matched control animals (n = 11) were used. Principal component analysis (PCA) distinguished signal corrected metabolite profiles from Lewis and LPK rats for kidney (PC-1 77%) and liver (PC-1 46%) tissue. There were marked differences in the metabolite profiles of the kidney tissues with 122 deconvoluted features significantly different between the LPK and Lewis strains. The metabolite profiles were less marked between strains for liver samples with 30 features significantly different. Five biochemical pathways showed three or more significantly altered metabolites: transcription/translation, arginine and proline metabolism, alpha-linolenic and linoleic acid metabolism, the citric acid cycle, and the urea cycle. The results of this study validate and complement the current literature and are consistent with the understood pathobiology of PKD.
AB - Polycystic kidney disease (PKD) encompasses a spectrum of inherited disorders that lead to end-stage renal disease (ESRD). There is no cure for PKD and current treatment options are limited to renal replacement therapy and transplantation. A better understanding of the pathobiology of PKD is needed for the development of new, less invasive treatments. The Lewis Polycystic Kidney (LPK) rat phenotype has been characterized and classified as a model of nephronophthisis (NPHP9, caused by mutation of the Nek8 gene) for which polycystic kidneys are one of the main pathologic features. The aim of this study was to use a GC–MS-based untargeted metabolomics approach to determine key biochemical changes in kidney and liver tissue of the LPK rat. Tissues from 16-week old LPK (n = 10) and Lewis age- and sex-matched control animals (n = 11) were used. Principal component analysis (PCA) distinguished signal corrected metabolite profiles from Lewis and LPK rats for kidney (PC-1 77%) and liver (PC-1 46%) tissue. There were marked differences in the metabolite profiles of the kidney tissues with 122 deconvoluted features significantly different between the LPK and Lewis strains. The metabolite profiles were less marked between strains for liver samples with 30 features significantly different. Five biochemical pathways showed three or more significantly altered metabolites: transcription/translation, arginine and proline metabolism, alpha-linolenic and linoleic acid metabolism, the citric acid cycle, and the urea cycle. The results of this study validate and complement the current literature and are consistent with the understood pathobiology of PKD.
KW - Gas chromatography
KW - Mass spectrometry
KW - Metabolomics
KW - Nephronophthisis
KW - Polycystic kidney disease
UR - http://www.scopus.com/inward/record.url?scp=85064311801&partnerID=8YFLogxK
U2 - 10.1016/j.jchromb.2019.04.021
DO - 10.1016/j.jchromb.2019.04.021
M3 - Article
C2 - 31005771
AN - SCOPUS:85064311801
SN - 1570-0232
VL - 1118-1119
SP - 25
EP - 32
JO - Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences
JF - Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences
ER -