A cell culture investigation of the mediation of compensatory renal growth

Hansen, Penelope Ann (1979) A cell culture investigation of the mediation of compensatory renal growth. Doctoral (PhD) thesis, Memorial University of Newfoundland.

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Abstract

Although the phenomenon of compensatory renal growth has been under inve3stigation for more than a century, its mediation has not been elucidated. The participation of a circulating, kidney-specific growth factor, either stimulatory of inhibitory, has been hypothesized, but tis existence has not been proved. Theoretical considerations predict that in vitro methods could be profitably used in these circumstances, since these methods would allow dissociation of the effects of the postulated factor from the complex physiological changes which accompany compensatory renal growth in vivo. – The work of this thesis consists of the development of a cell culture system suitable for testing serum from previously uninephrectomized or sham-operated animals for the presence of such a growth factor. A method of primary culture of adult Fischer rat kidney epithelium is described. The morphology of these cultured cells is compatible with that of proximal tubule epithelium in site, these being the cells stimulated to divide in vivo by uninephrectomy. The chief finding reported in this thesis is that treatment with serum from rats uninephrectomized 48 hours previously results in consistent, significant increase in uptake of tritiated thymidine by cultures, when compared with control sera from sham-operated rats. Serum from rats uninephrectomized 18-36 hours previously is not consistently stimulatory. Preliminary investigation with this culture system indicates that: (a) the differential effect of control and uninephrectomy sera is due to the presence of a stimulatory factor in the latter rather than an inhibitor in the former; (b) soluble fractions of homogenates of both kidney and liver tissue exhibit inhibitory dose-effects in cultures; (c) xanthopterin, a compound that stimulates kidney tubule epithelial cell division in vivo, has no stimulatory effect in vitro; (d) serum obtained from human kidney transplant donors 24-72 hours after uninephrectomy stimulates increasing thymidine uptake in cultures. – Use of this cultures system has confirmed the existence of a serum factor involved in compensatory renal growth, and should prove to be a valuable tool for its characterization.

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