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Published on: November 2, 2015
Cellular response to renal hypoxia is different in adolescent and infant rats
Shinsuke Adachi1, Sergey Zelenin, Yasutaka Matsuo
1Astrid Lindgren Children's Hospital, S-171 76 Stockholm, Sweden.
Insights
Immature kidneys show greater tolerance to ischemia and reperfusion injury than mature kidneys. This is due to developmental differences in cellular responses, including Na(+)-K(+)-ATPase regulation and protective factor expression.
Area of Science:
- Nephrology
- Developmental Biology
- Cellular Physiology
Background:
- Immature renal tubules exhibit higher tolerance to ischemic injury compared to mature tubules.
- Understanding the cellular mechanisms underlying this developmental difference is crucial for treating kidney injury.
Purpose of the Study:
- To compare the developmental patterns of cellular responses to hypoxia and reoxygenation in immature and mature rat renal proximal tubules.
- To investigate the role of Na(+)-K(+)-ATPase, micro-calpain, and heme oxygenase-1 in differential ischemic tolerance.
Main Methods:
- Primary cultured renal proximal tubular cells from 10- and 40-day-old rats were used.
- Confocal microscopy assessed Na(+)-K(+)-ATPase redistribution.
- RT-PCR measured the expression of Na(+)-K(+)-ATPase, micro-calpain, and heme oxygenase-1 in rat renal cortex.
Main Results:
- Mature kidney cells showed a ~2-fold greater redistribution of Na(+)-K(+)-ATPase from the plasma membrane during hypoxia compared to immature cells.
- Reoxygenation fully restored Na(+)-K(+)-ATPase in immature cells, but not mature cells.
- Immature kidneys had lower micro-calpain and higher heme oxygenase-1 expression, suggesting protective mechanisms.
Conclusions:
- Developmental differences in Na(+)-K(+)-ATPase regulation and expression of injury-related proteins contribute to the immature kidney's enhanced tolerance to ischemia-reperfusion injury.
- Lower micro-calpain and higher heme oxygenase-1 expression in immature kidneys play a protective role against ischemic damage.
Abstract:
Immature renal tubules are more tolerant to ischemia than mature renal tubules. Here we compared the developmental pattern for some cellular responses evoked by hypoxia and reoxygenation in renal proximal tubules from 10- and 40-day-old rats. Redistribution of Na(+)-K(+)-ATPase from the plasma membrane was studied by confocal microscopy techniques in primary cultured renal proximal tubular cells. The developmental expression of Na(+)-K(+)-ATPase, micro-calpain and heme oxygenase-1 was measured by RT-PCR techniques in rat renal cortex. In response to hypoxia Na(+)-K(+)-ATPase redistribution from the plasma membrane was almost 2-fold increased in cells isolated from mature kidneys compared with cells isolated from immature kidneys. Reoxygenation resulted in a complete reestablishment of Na(+)-K(+)-ATPase in the plasma membrane in the immature but not in the mature cells. The dissociation of Na(+)-K(+)-ATPase from the plasma membrane was associated with a reduced activity and a reduced expression of Na(+)-K(+)-ATPase in the mature but not in the immature tubular cells. The expression of micro-calpain, a factor shown to induce ischemic injury to proximal tubular cells, was significantly lower in the immature compared with the mature kidney, whereas the expression of heme oxygenase-1, a factor shown to protect from renal ischemic injury, was significantly higher in the immature kidney. The results help to explain the increased tolerance of the immature kidney to injury caused by ischemia and reperfusion.
