Cellular biology of tubulointerstitial growth.
The study of tubular growth has certainly become more complex since Pierre-Rayers's time and is progressing toward a molecular dissection of regulatory events. Understanding the mechanisms of tubular growth is important, because these cells represent the bulk of the nephron, and there is convincing evidence of a link between tubular hypertrophy and the progression of renal disease with irreversible tubulointerstitial fibrosis as an end point. Two tubular growth responses can be distinguished: hypertrophy and hyperplasia. These fundamentally different patterns of growth indicate that diverse molecular mechanisms may be involved in inducing distinct growth responses. It is likely that cytokines and polypeptide growth factors play a role in tubular hypertrophy and hyperplasia. Probably, a combination of growth factors including inhibitory polypeptides like TGF beta, rather than a single factor, is necessary for differentiated tubular growth responses. Such factors bind to their receptors, and signals are transduced to the nucleus by various second messengers involving protein kinases, cyclic nucleotides, Ca++, and inositolphosphates. The phosphorylation of nuclear trans-acting factors resulting in an expression of immediate early genes may be the common pathway of many of these mediators. Finally, whether the cell is to proliferate or to remain in the G1-phase of the cell cycle is determined by the very complex cascade phosphorylation of kinases and their associations with different cyclins. How the induction of immediate early genes is linked to events of the cell cycle is currently incompletely understood. Negative regulation of growth through protein growth suppressors like the retinoblastoma gene product or the expression of special genes only during cell rest may be mandatory for the fine tuning of tubular growth.
Wolf
G
G
Department of Internal Medicine, University of Frankfurt, Germany.
Neilson
E G
EG
D001483:Base Sequence; D002453:Cell Cycle / Q000502:physiology; D005109:Extracellular Matrix / Q000502:physiology*; D017781:Genes, Immediate-Early; D006133:Growth Substances; D006801:Humans; D006965:Hyperplasia; D006984:Hypertrophy; D007684:Kidney Tubules / Q000166:cytology* / Q000254:growth & development* / Q000473:pathology; D008969:Molecular Sequence Data; D011519:Proto-Oncogenes; D015398:Signal Transduction
D006133:Growth Substances