NDLI: Developmental regulation and the role of insulin and insulin receptor in metanephrogenesis

Content Provider	PubMed Central
Author	Liu, Zheng Z. Kumar, Anil Ota, Kosuke Wallner, Elisabeth I. Kanwar, Yashpal S.
Copyright Year	1997
Abstract	The insulin family of peptides and their receptors influence cellular growth in very early preimplantation embryos. In this study their expression and role in renal organogenesis was investigated. By immunofluorescence microscopy and in situ hybridization, insulin receptor (IR) expression was seen in the ureteric bud branches and early nephron precursors in mouse metanephroi harvested at day 13 of gestation. The expression gradually decreased in successive stages of gestation, and it was confined mainly to renal tubules in 1-week-old mice. Similar developmental regulation of the IR and insulin was observed by reverse transcriptase–polymerase chain reaction (RT-PCR) analyses. Addition of insulin into the culture medium at low concentrations, ranging from 40 to 400 ng/ml, induced trophic changes and increased [3H]thymidine incorporation in the embryonic renal explants, and inclusion of IR β-subunit-specific antisense oligodeoxynucleotide caused marked dysmorphogenesis and growth retardation of the metanephroi. Specificity of the antisense effect was reflected by immunoprecipitation experiments in which translational blockade of the β subunit of the IR was observed. RT-PCR analyses revealed that the α subunit of the IR was unaffected by the antisense treatment of metanephric explants. Concomitantly, de novo synthesis of morphogenetic regulatory extracellular matrix proteins, especially the proteoglycans, was decreased. Gel-shift analyses indicated a failure in the activation of c-fos promoter region binding protein(s) by insulin in the antisense oligodeoxynucleotide-treated explants. These studies suggest that insulin and its putative receptor are developmentally regulated in the murine embryonic metanephros, and they play a role in renal organogenesis, possibly by affecting other modulators of morphogenesis—i.e., extracellular matrix proteins and protooncogenes.
Starting Page	6758
File Format	PDF
ISSN	10916490
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	13
Volume Number	94
Language	English
Publisher	The National Academy of Sciences of the USA
Publisher Date	1997-06-24
Access Restriction	Open
Rights Holder	The National Academy of Sciences of the USA
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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