Abstract
BackgroundNetrin-1 is a laminin-related secreted protein, is highly induced after tissue injury, and may serve as a marker of injury. However, the regulation of netrin-1 production is not unknown. Current study was carried out in mouse and mouse kidney cell line (TKPTS) to determine the signaling pathways that regulate netrin-1 production in response to injury.Methods and Principal FindingsIschemia reperfusion injury of the kidney was induced in mice by clamping renal pedicle for 30 minutes. Cellular stress was induced in mouse proximal tubular epithelial cell line by treating with pervanadate, cisplatin, lipopolysaccharide, glucose or hypoxia followed by reoxygenation. Netrin-1 expression was quantified by real time RT-PCR and protein production was quantified using an ELISA kit. Cellular stress induced a large increase in netrin-1 production without increase in transcription of netrin-1 gene. Mitogen activated protein kinase, ERK mediates the drug induced netrin-1 mRNA translation increase without altering mRNA stability.ConclusionOur results suggest that netrin-1 expression is suppressed at the translational level and MAPK activation leads to rapid translation of netrin-1 mRNA in the kidney tubular epithelial cells.
Highlights
Netrin-1 is a laminin-related secreted protein that is widely expressed in many tissues, including kidney [1,2]
Our results suggest that netrin-1 expression is suppressed at the translational level and mitogen activated protein kinases (MAPK) activation leads to rapid translation of netrin-1 mRNA in the kidney tubular epithelial cells
Our results showed that netrin-1 is rapidly translated in tubular epithelial cells, which is regulated by stress-activated MAPK pathways
Summary
Netrin-1 is a laminin-related secreted protein that is widely expressed in many tissues, including kidney [1,2]. Netrin-1 was shown to regulate neuronal migration [3], inflammation during ischemia reperfusion injury of the kidney [1,4,5], lung [6], whole animal hypoxia [7], cisplatin induced kidney injury [8], angiogenesis during development [9], and in adult heart [10]. Netrin-1 is a laminin-related secreted protein, is highly induced after tissue injury, and may serve as a marker of injury. Current study was carried out in mouse and mouse kidney cell line (TKPTS) to determine the signaling pathways that regulate netrin-1 production in response to injury
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