Too much protein taken up by kidney receptors leads to increased cell growth and aging in kidney tubules of protein-leaking mice, mainly in the outer kidney region

Protein overload in proximal tubular epithelial cells (PTECs) is associated with increased proliferation and cellular senescence.

• Treatment with human serum albumin carrying fatty acids promoted both proliferation and senescence in human immortalized proximal tubular cells.
• In proteinuric podocin-knockout mice, significant increases in markers of proliferation and senescence were observed, particularly in the outer medulla.
• The response in podocin-KO mice was markedly reduced in mice lacking the ability to endocytose proteins.
• Increased levels of certain cytokines known to stimulate proliferation and senescence were noted in podocin-KO mice, but these levels were reduced in triple-KO mice.
• Inhibition of TGF-β receptors prevented the senescence induced by human serum albumin, while recombinant TGF-β was sufficient to induce senescence in the cells.

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