Growth hormone (GH)-transgenic insulin-like growth factor 1 (IGF1)-deficient mice allow dissociation of excess GH and IGF1 effects on glomerular and tubular growth

Blutke, Andreas; Schneider, Marlon R.; Wolf, Eckhard und Wanke, Rüdiger (2016): Growth hormone (GH)-transgenic insulin-like growth factor 1 (IGF1)-deficient mice allow dissociation of excess GH and IGF1 effects on glomerular and tubular growth. In: Physiological Reports, Bd. 4, Nr. 5, e12709

Abstract

Growth hormone (GH)-transgenic mice with permanently elevated systemic levels of GH and insulin-like growth factor 1 (IGF1) reproducibly develop renal and glomerular hypertrophy and subsequent progressive glomerulosclerosis, finally leading to terminal renal failure. To dissociate IGF1-dependent and -independent effects of GH excess on renal growth and lesion development in vivo, the kidneys of 75 days old IGF1-deficient (I-/-) and of IGF1-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 IGF1. In contrast, IGF1 represents an important mediator of GH-dependent proximal tubular growth in GH-transgenic mice.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Chemie und Pharmazie > Department Biochemie
• Themengebiete: 500 Naturwissenschaften und Mathematik > 540 Chemie
• ISSN: 2051-817X
• Sprache: Englisch