Open AccessGrowth hormone ( GH )‐transgenic insulin‐like growth factor 1 ( IGF 1)‐deficient mice allow dissociation of excess GH and IGF 1 effects on glomerular and tubular growth
Author(s) -
Blutke Andreas,
Schneider Marlon R.,
Wolf Eckhard,
Wanke Rüdiger
Publication year - 2016
Publication title -
physiological reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 39
ISSN - 2051-817X
DOI - 10.14814/phy2.12709
Subject(s) - medicine , endocrinology , podocyte , genetically modified mouse , glomerulosclerosis , muscle hypertrophy , hyperplasia , transgene , renal hypertrophy , growth factor , insulin like growth factor , kidney , biology , diabetic nephropathy , proteinuria , receptor , biochemistry , gene
Growth hormone ( GH )‐transgenic mice with permanently elevated systemic levels of GH and insulin‐like growth factor 1 ( IGF 1) reproducibly develop renal and glomerular hypertrophy and subsequent progressive glomerulosclerosis, finally leading to terminal renal failure. To dissociate IGF 1‐dependent and ‐independent effects of GH excess on renal growth and lesion development in vivo, the kidneys of 75 days old IGF 1‐deficient ( I −/− ) and of IGF 1‐deficient GH ‐transgenic mice ( I −/− /G ), as well as of GH ‐transgenic ( G ) and nontransgenic wild‐type control mice ( I +/+ ) were examined by quantitative stereological and functional analyses. Both G and I −/− /G mice developed glomerular hypertrophy, hyperplasia of glomerular mesangial and endothelial cells, podocyte hypertrophy and foot process effacement, albuminuria, and glomerulosclerosis. However, I −/− /G mice exhibited less severe glomerular alterations, as compared to G mice. Compared to I +/+ mice, G mice exhibited renal hypertrophy with a significant increase in the number without a change in the size of proximal tubular epithelial ( PTE ) cells. In contrast, I −/− /G mice did not display significant PTE cell hyperplasia, as compared to I −/− mice. These findings indicate that GH excess stimulates glomerular growth and induces lesions progressing to glomerulosclerosis in the absence of IGF 1. In contrast, IGF 1 represents an important mediator of GH ‐dependent proximal tubular growth in GH ‐transgenic mice.