A recent study suggests that reducing salt and body fluid levels can trigger kidney regeneration and repair in mice. This natural regenerative response is driven by a specific group of kidney cells located in the macula densa (MD) region, which play a crucial role in sensing salt levels and regulating key functions like filtration and hormone secretion in the kidney.
The study delves into the evolution of healthy kidneys from simpler fish kidney structures to more advanced and efficient ones capable of absorbing higher amounts of salt and water. By feeding lab mice a low-salt diet supplemented with an ACE inhibitor, which further reduces salt and fluid levels, researchers observed regenerative activity in the MD region. They also found that interfering with signals sent by the MD cells hindered the regeneration process, highlighting the pivotal role of these cells in orchestrating kidney repair.
Further analysis of the mouse MD cells revealed similarities to nerve cells in terms of genetic and structural features. This resemblance is noteworthy as nerve cells are known to regulate organ regeneration, such as in the skin.
Specific signals from genes like Wnt, NGFR, and CCN1 identified in the mouse MD cells could be enhanced through a low-salt diet to promote kidney structure and function regeneration. Notably, the activity of CCN1 was found to be diminished in patients with chronic kidney disease (CKD).
Testing the therapeutic potential of these findings, the researchers administered CCN1 to mice with focal segmental glomerulosclerosis, a type of CKD, and treated them with MD cells cultured in low-salt conditions. Both approaches proved successful, with MD cell treatment yielding the most significant improvements in kidney structure and function, possibly due to the secretion of additional factors besides CCN1 that support kidney regeneration.
The study, led by Professor Peti-Peterdi from the Keck School of Medicine of USC, aims to develop a new therapeutic approach for kidney disease, which affects a substantial portion of the global population. By focusing on the regenerative mechanisms inherent in healthy kidneys, the researchers hope to pave the way for innovative treatments for kidney ailments.
The study received federal funding from the National Institutes of Health and support from the American Heart Association. The authors have disclosed potential conflicts of interest related to their involvement in a biotechnology company dedicated to developing regenerative treatments for CKD.
