The transcriptome of early compensatory kidney growth reveals cell and time specific responses
Darling M. Rojas-Canales,
Soon Wei Wong,
Elise J. Tucker,
Anthony O. Fedele,
Kym McNicholas,
Anne-Sophie Mehdorn,
Jonathan M. Gleadle
Affiliations
Darling M. Rojas-Canales
Department of Renal Medicine, Southern Adelaide Local Health Network, Flinders Medical Centre, Bedford Park, SA, Australia; Flinders University, College of Medicine and Public Health, Flinders Health and Medical Research Institute, Adelaide, SA, Australia
Soon Wei Wong
Department of Renal Medicine, Southern Adelaide Local Health Network, Flinders Medical Centre, Bedford Park, SA, Australia; Flinders University, College of Medicine and Public Health, Flinders Health and Medical Research Institute, Adelaide, SA, Australia
Elise J. Tucker
Flinders University, College of Medicine and Public Health, Flinders Health and Medical Research Institute, Adelaide, SA, Australia
Anthony O. Fedele
Department of Renal Medicine, Southern Adelaide Local Health Network, Flinders Medical Centre, Bedford Park, SA, Australia
Kym McNicholas
Flinders University, College of Medicine and Public Health, Flinders Health and Medical Research Institute, Adelaide, SA, Australia
Anne-Sophie Mehdorn
Flinders University, College of Medicine and Public Health, Flinders Health and Medical Research Institute, Adelaide, SA, Australia; Department of General, Abdominal, Thoracic, Transplantation and Paediatric Surgery, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany
Jonathan M. Gleadle
Department of Renal Medicine, Southern Adelaide Local Health Network, Flinders Medical Centre, Bedford Park, SA, Australia; Flinders University, College of Medicine and Public Health, Flinders Health and Medical Research Institute, Adelaide, SA, Australia; Corresponding author
Summary: Following kidney removal, the remaining kidney enlarges and increases its function. The mechanism and signals driving this compensatory kidney hypertrophy and the enlargement of its constituent kidney cells remains elusive. RNA-seq studies in mice undergoing hypertrophy 24, 48, and 72 h following nephrectomy were undertaken to understand the early transcriptional changes. This revealed substantial enhancement of cholesterol biosynthesis pathways, increases in mitochondrial gene expression and cell cycle perturbations. Single nuclei RNA-seq delineated cell specific changes at 24 h post nephrectomy and showed that sterol binding protein 2 (SREBP2) activity increases in medullary thick ascending limb cells in keeping with promotion of cholesterol synthesis. Cultured renal tubular cells were examined for insulin-like growth factor-1 (IGF-1) stimulated hypertrophy and SREBP2 was found to be required for increase in cell size. This work describes the early cell specific growth pathways mediating cellular and kidney hypertrophy with an intriguing role for cholesterol synthesis.
