MESSAI.iO

AI summary

75% confidence

This study identifies the E3 ligase Pellino1 (Peli1) as a critical driver of autosomal dominant polycystic kidney disease (ADPKD) pathogenesis under inflammatory conditions. The research demonstrates that Peli1 overexpression, induced by TLR stimulation, impairs renal function and accelerates cyst formation in transgenic mice. Mechanistically, elevated Peli1 promotes epithelial cell proliferation by stabilizing S6K1 to activate the mTOR signaling axis.

Generated by MESSAI extraction pipeline · review against source PDF

Extraction

Reported parameters

125 extracted values

View extracted values

No 3D model is mapped to this paper yet. Parameter ranges above still place reported values on the literature distribution.

What they did

System
not_BES

What worked

No outcome metrics extracted yet.

Abstract

Abstract Ubiquitination serves a critical role in regulating both inflammatory responses and kidney injury. Among inherited renal disorders, autosomal dominant polycystic kidney disease (ADPKD) has demonstrated associations with disrupted ubiquitin signaling that exacerbates inflammation and cyst progression. In this study, we demonstrate that the E3 ligase Pellino1 (Peli1) acts as an essential contributor to the pathogenesis of ADPKD amid inflammatory conditions. In individuals with clear cell renal cell carcinoma (ccRCC), Peli1 exhibits markedly elevated expression, and this upregulation is associated with adverse clinical outcomes. Additionally, we find that various TLR stimulations in renal tubular cells induce increased Peli1 expression, which is also elevated in samples from ADPKD patients. Using doxycycline-inducible Peli1-transgenic mice, we establish that Peli1 overexpression leads to impaired renal function and facilitates cyst formation. On a mechanistic level, elevated Peli1 promotes cystic epithelial cell proliferation by activating mTOR signaling, accomplished through the stabilization of S6K1. In summary, our data indicate that TLR-driven upregulation of Peli1 facilitates renal cyst growth via S6K1 stabilization. These results reveal a novel mechanistic link between PKD and ccRCC.

Key findings

  • Pellino1 (Peli1) expression is markedly elevated in clear cell renal cell carcinoma (ccRCC) and correlates with adverse clinical outcomes.
  • TLR stimulations in renal tubular cells induce increased Peli1 expression, which is also observed in samples from ADPKD patients.
  • Inducible overexpression of Peli1 in mice leads to impaired renal function and facilitates cyst formation.

Keywords

Autosomal dominant polycystic kidney diseasePathogenesisDownregulation and upregulationUbiquitin ligasePolycystic kidney diseaseKidney

Identifiers

DOI
10.1038/s41419-026-08479-6
Journal
Cell Death & Disease
Year
2026