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Excessive protein uptake by endocytic receptors causes elevated proliferation and senescence in proximal tubules primarily in outer medulla of proteinuric mice

Year: 2026
Type: article
Abstract: This study identifies the outer medulla as a critical spot where protein overload triggers a pathological cycle of proliferation and cellular senescence in proximal tubular epithelial cells (PTECs). By using a unique triple-knockout model, we demonstrate that protein endocytosis, rather than luminal protein presence alone, is the essential driver of this response through changes in the cytokine profile. We establish that TGF-β-dependent pathways are activated in response to protein overload, which may contribute to proliferation and senescence.
DOI: 10.1152/ajprenal.00123.2026
Authors: Yoshifumi Kurosaki, Fumitaka Kawakami, Akemi Imoto, Naokazu Sato, Motoshi Ouchi, Asuka Morita, Kathrin Weyer, Géraldine Mollet, Rei Kawashima, Yoshiko Iizuka, Takafumi Ichikawa, Tsuneo Takenaka, Rikke Nielsen, Naohito Ishii
Institutions: Kitasato University, Chiba University, Dokkyo Medical University, Aarhus University, Université Paris Cité, International University of Health and Welfare
Language: English
Subfield: Nephrology
Field: Medicine
Open Access status: hybrid
OpenAlex ID: W7171845382
FWCI: 4.727
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Cited by: 1
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