The same cell type can help or hinder kidney repair after an acute injury


A mouse kidney one month after acute kidney injury. Cells that proliferated in response to the lesion are shown in green. Credit: Louisa MS Gerhardt / McMahon Lab

Andy McMahon’s USC Stem Cell Laboratory has identified a type of injured cell that could contribute to the transition from acute kidney injury to chronic kidney disease, as described in a new published study at the Proceedings of the National Academy of Sciences (PNAS).

“Acute kidney injury can be a common side effect of surgery, sepsis or true , and there is no effective treatment, “said McMahon, who is WM Keck Provost and a university professor of stem cell biology and regenerative medicine and biological sciences at USC.” Even a mild or moderate injury can progress , which affects 9.1% of the world’s population and causes 1.2 million deaths each year. “

The adult kidney has no stem cells to regenerate damaged tissue in its approximately 1 million filter units, called nephrons. Damage occurs primarily in a segment of the nephron known as the proximal tubule. Fortunately, differentiated proximal tubule cells (PTCs) have their own repair capacity.

The repair process

To understand this repair process, early authors Louisa MS Gerhardt, Jing Liu, and colleagues at McMahon Laboratory pioneered a way to track injured PTCs in laboratory mice by using a protein called keratin. -20, which cells tend to produce later .

As expected, when a sudden injury resulted in the death of some PTCs, survivors multiplied to repair the injury. Still, weeks later was restored, the scientists observed that PTCs, which could not be repaired normally, appeared at the site of the original lesion and also in regions far from the initial lesion. Unlike normal PTCs, these damaged cells showed gene network activity involved in inflammation, scarring, and – characteristics associated with a slow progression to chronic kidney disease.


Credit: Pixabay / CC0 Public Domain

How damaged PTCS can promote disease progression

Some of the harmful PTCs showed activity in both genes that support survival and in genes that promote programmed cell death, the normal process by which irreparably damaged cells self-destruct. As observed in cancers, pro-survival genes can prevent programmed cell death, despite abnormalities that normally limit cell survival, making them more likely to be damaged. endure, promote .

“This research presents a dynamic picture of how the initial injury, even if mild, leads to the creation of harmful PTCs that are likely to contribute to chronic kidney disease,” said McMahon, who is also the director of the Broad Center. regeneration Eli and Edythe. Stem cell medicine and research at USC. “Our study also raises the possibility of targeting these PTCs that are harmful to their destruction, either by preparing them for immune attack or by eliminating genes that interfere with the normal protection of those programmed. . “

The same number of PNAS it also includes an accompanying Q&A with McMahon to mark his recent election as a member of the National Academy of Sciences.

The study examines the effects of COVID-19 on human kidney cells

More information:
Louisa MS Gerhardt et al., “Monoclear transcriptomics reveals diversity of proximal tubule cell states in a dynamic response to acute renal injury.” PNAS (2021).

Citation: The same cell type can help or hinder kidney repair after an acute injury (2021, June 21) recovered on June 21, 2021 at cell-hinder-kidney-acute-injury.html

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