Abstract
During postnatal maturation, the proximal tubule undergoes rapid growth, initially mainly hyperplastic, later hypertrophic. The mechanism behind the reduction of hyperplastic growth is unknown. Proliferation was studied in proximal tubule cells (PTC) from infant (I) and adolescent (A) rats after 2 days in primary culture and analyzed by 3H-thymidine autoradiography. The rate of proliferation was determined as the percentage labelled nuclei (LI).
The cells grew in colonies with contact inhibited central cells and rapidly growing peripheral cells. The growth rate was determined in each layer of cells from periphery (layer 1) to center (layers 5-6). In layer 1 I and A cells proliferate at the same rate (44 ± 4% vs 41 ± 4% NS). Moving into the center proliferation in A cells fell faster than in I cells. Compared to layer 1, proliferation in layers 5-6 was inhibited by 87 ± 4% in A cells whereas in I cells by 59±5% (p<0.05).
To investigate possible mechanisms explaining the low degree of contact inhibition in I cells, we tested their sensitivity to growth factors. Removing serum from the culture medium lead to a more marked inhibition of I than A central cells (84±5% vs 54 ± 5% p<0.05). TGFβ1 (0.1 pM), a well characterized inhibitor of epithelial growth, inhibited I central cells by 66 ±7% whereas no significant effect was seen in A cells.
Conclusion: An increasing contact inhibition in rat PTC may explain the postnatal reduction in hyperplastic growth. A reduced sensitivity to growth stimulatory factors rather than an increased sensitivity to growth inhibitors is suggested.
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Bratt, E., Aperia, A. & Larsson, S. A POSTNATAL INCREASE IN CONTACT INHIBITION REDUCES HYPERPLASTIC GROWTH IN RENAL EPITHELIAL CELLS. Pediatr Res 32, 624 (1992). https://doi.org/10.1203/00006450-199211000-00117
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DOI: https://doi.org/10.1203/00006450-199211000-00117