Signal Discovered that Induces Lone Kidney Growth when other is Lost

ENLARGEMENT of a lone kidney following the loss of its partner has finally been explained, as scientists have identified a signal that could be the catalyst to an oft-observed phenomenon.

When one kidney is removed due to injury or transplantation, the remaining kidney can quickly become 50-60% larger, likely triggered by the need to compensate for its partner’s absence. Now scientists have discovered that the increased blood flow to the kidney, which occurs when the other is lost, also delivers substantially more of the protein-building amino acids (AAs). This activates mTORC1, which triggers the growth. “For a cell to grow bigger, it has to have increased protein synthesis, which is regulated by mTORC1,” said Dr Jian-Kang Chen, co-corresponding study author and a pathologist and kidney researcher, Medical College of Georgia, Georgia Regents University, Augusta, Georgia, USA.

In the kidneys, mTORC1 normally functions as a key regulator of protein synthesis and cell growth. When one kidney is lost, mTORC1 detects the increased arrival of AAs to the remaining kidney, and creates more protein upon stimulation by its upstream messenger enzyme called Class III phosphatidylinositol 3-kinase, or PI3K. Tying off one kidney in a mouse caused the immediate increase of blood flow to the remaining kidney, as did AA availability and mTORC1 activation. Follow-up studies suggested that growth typically plateaus at 50-60% within approximately 3 months.

Other mice models missing the PTEN gene, which produces a protein that regulates cell division and growth, also indicated mTORC1 as the growth driver. The activation pathway was slightly different, however, as sibling complex mTORC2 was activated by gene removal, eventually activating mTORC1. It is interesting to note that mTORC1 did not need mTORC2 to become activated upon kidney removal from the PTEN knockout. The same applied in the other model, in which a kidney was removed but PTEN was not. The importance of Class III PI3K in mTORC1 activation is thus apparent. Both kidneys grew larger in the absence of PTEN. When rapamycin was introduced, which inhibits mTORC1, both kidneys became smaller.

The researchers are determined to learn more about why the hypertrophy appears to stop at a certain point and whether the significantly increased width of many kidneys is ultimately detrimental to kidney function. By discovering more about growth triggers, they hope to eventually be able to intervene to restrict the response and help ensure that the lone kidney continues to perform adequately.

(Image: freeimages.com)

Comments are closed.