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A Mouse 5/6th Nephrectomy Model That Induces Experimental Uremic Cardiomyopathy
Published on: November 7, 2017
Specific gene expression during compensatory renal hypertrophy in the rat
Abstract:
The compensatory growth of the kidney which is induced by unilateral nephrectomy is a highly regulated process resulting principally in hypertrophy of the remaining kidney. The events which regulate this process are unknown. We have examined the levels of transcripts for the proto-oncogenes, myc, H-ras, K-ras, and fos, and the cellular genes, H4 histone, ornithine aminotransferase, and gamma-glutamyl transpeptidase, following unilateral nephrectomy in the rat. The pattern of expression of c-myc, c-H-ras, and c-K-ras during compensatory growth of the kidney differs from the pattern of expression of these proto-oncogenes during liver regeneration, in which, unlike the kidney, hyperplasia rather than hypertrophy predominates. The lack of change in the abundance of these proto-oncogene transcripts following unilateral nephrectomy suggests a primary relationship between the expression of these proto-oncogenes and DNA synthesis and indicates there may be separate signals for cell growth, one to double cell size and one to replicate DNA. Increased mRNA transcripts for the enzymes ornithine aminotransferase and gamma-glutamyl transpeptidase were induced in the contralateral kidney after nephrectomy. The time course of expression for these two enzymes differs. The early expression of the gamma-glutamyl transpeptidase gene may indicate an involvement of this glutathione-metabolizing enzyme during renal compensatory growth, while the function of the delayed increase in ornithine aminotransferase transcripts in the remaining kidney is not apparent.
Insights
Compensatory kidney growth after surgery involves cell enlargement, not division. Proto-oncogene expression differs from liver regeneration, suggesting distinct growth signals for cell size and DNA replication.
Area of Science:
- Nephrology
- Molecular Biology
- Cellular Biology
Background:
- Compensatory kidney growth after unilateral nephrectomy is a regulated process.
- The specific molecular events regulating this kidney hypertrophy remain largely unknown.
Purpose of the Study:
- To investigate the expression patterns of key proto-oncogenes and cellular genes during compensatory kidney growth.
- To compare gene expression during kidney hypertrophy with that during liver regeneration.
Main Methods:
- Unilateral nephrectomy was performed on rats.
- Quantitative analysis of transcript levels for c-myc, c-H-ras, c-K-ras, c-fos, H4 histone, ornithine aminotransferase, and gamma-glutamyl transpeptidase was conducted.
Main Results:
- Proto-oncogene expression (c-myc, c-H-ras, c-K-ras) did not significantly change, unlike in liver regeneration where hyperplasia predominates.
- Increased mRNA transcripts for ornithine aminotransferase and gamma-glutamyl transpeptidase were observed in the remaining kidney.
- The expression patterns suggest proto-oncogenes are linked to DNA synthesis, potentially indicating separate signals for cell growth and DNA replication.
Conclusions:
- Compensatory kidney hypertrophy appears to be regulated by distinct molecular mechanisms compared to liver regeneration.
- The findings suggest separate signaling pathways control cell size increase versus DNA replication during kidney compensatory growth.
- Gamma-glutamyl transpeptidase may play a role in early renal compensatory growth, while the function of increased ornithine aminotransferase remains unclear.

