LIM kinase function and renal growth: Potential role for LIM kinases in fetal programming of kidney development

Sparrow, Alexander J.; Sweetman, Dylan; Welham, Simon

doi:10.1016/j.lfs.2017.07.034

Cited by 2 publications

(1 citation statement)

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“…The two major causes of acute kidney injury are ischemic and nephrotoxic damages that may induce a loss of renal function and consequent pathological alterations, such as tubular dilatation, loss of renal microvilli, apoptosis, and even necrosis [46]. Cell density in the proximal tubules indicates the developmental status of renal epithelial cells in nephrogenesis [47]. The number of proximal tubular epithelial cells in adult mice was significantly decreased following neonatal hyperoxia in the current study.…”

Section: Discussionmentioning

confidence: 64%

Proximal Tubular Development Is Impaired with Downregulation of MAPK/ERK Signaling, HIF-1α, and Catalase by Hyperoxia Exposure in Neonatal Rats

You

2019

Oxidative Medicine and Cellular Longevity

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Supplemental oxygen therapy (hyperoxia) is a widely used treatment for alveolar hypoxia in preterm infants. Despite being closely monitored, hyperoxia exposure is believed to undermine neonatal nephrogenesis and renal function caused by elevated oxidative stress. Previous studies have mostly focused on the hyperoxia-induced impairment of glomerular development, while the long-term impact of neonatal hyperoxia on tubular development and the regulatory component involved in this process remain to be clarified. Here, we examined tubular histology and apoptosis, along with the expression profile of mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) signaling, hypoxia-inducible factor 1α (HIF-1α), and catalase, following hyperoxia exposure in neonatal rats. Hematoxylin and eosin (H&E) staining revealed the early disappearance of the nephrogenic zone, as well as dilated lumens and reduced epithelial cells, of mature proximal tubules following neonatal hyperoxia. A robust increase in tubular cell apoptosis caused by neonatal hyperoxia was found using a TUNEL assay. Moreover, neonatal hyperoxia altered renal MAPK/ERK signaling activity and downregulated the expression of HIF-1α and catalase in the proximal tubules throughout nephrogenesis from S-shaped bodies to mature proximal tubules. Cell apoptosis in the proximal tubules was positively correlated with HIF-1α expression on the 14th postnatal day. Our data indicates that proximal tubular development is impaired by neonatal hyperoxia, which is accompanied by altered MAPK/ERK signaling as well as downregulated HIF-1α and catalase. Therapeutic management that targets MAPK/ERK signaling, HIF-1α, or catalase may serve as a protective agent against hyperoxia-induced oxidative damage to neonatal proximal tubules.

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Section: Discussionmentioning

confidence: 64%