Key result
Deficiency of scavenger receptors Stabilin-1 and Stabilin-2 in mice leads to age-dependent renal and hepatic deposition of TGFBI and Periostin, resulting in glomerulofibrosis and reduced lifespan.
Deficiency of Stabilin-1 and Stabilin-2 leads to age-dependent renal and hepatic deposition of TGFBI and POSTN due to impaired hepatic scavenging, contributing to organ dysfunction in mice.
Answers are grounded in this paper and cite their sources.
Stabilin deficiency promotes renal and hepatic fibrosis in mice; leaves open whether this pathway contributes to human disease.
Background Stabilin-1 and Stabilin-2 are two major scavenger receptors of liver sinusoidal endothelial cells that mediate removal of diverse molecules from the plasma. Double-knockout mice (Stab-DKO) develop impaired kidney function and a decreased lifespan, while single Stabilin deficiency or therapeutic inhibition ameliorates atherosclerosis and Stab1-inhibition is subject of clinical trials in immuno-oncology. Although POSTN and TFGBI have recently been described as novel Stabilin ligands, the dynamics and functional implications of these ligands have not been comprehensively studied. Methods Immunofluorescence, Western Blotting and Simple Western™ as well as in situ hybridization (RNAScope™) und qRT-PCR were used to analyze transcription levels and tissue distribution of POSTN and TGFBI in Stab-KO mice. Stab-POSTN-Triple deficient mice were generated to assess kidney and liver fibrosis and function in young and aged mice. Results TGFBI and POSTN protein accumulated in kidney and liver tissue in Stab-DKO mice during aging despite unchanged transcriptional levels. Stab-POSTN-Triple KO mice showed glomerulofibrosis and a reduced lifespan comparable to Stab-DKO mice. However, alterations of the glomerular diameter and vascular density were partially normalized in Stab-POSTN-Triple KO. Conclusion TGFBI and POSTN are Stabilin-ligands that are deposited in an age-dependent manner in the kidneys and liver due to insufficient scavenging in the liver. Functionally, POSTN appears to partially contribute to the observed renal phenotype in Stab-DKO mice. This study provides details on downstream effects how how Stabilin dysfunction affects distant organs on a molecular and functional level.
No takes yet. Share an insight, caveat, or question.
Leibing et al. (2023) studied Stabilin deficiency. Stabilin-1 and Stabilin-2 double knockout vs. Wild-type mice was evaluated on Renal and hepatic deposition of TGFBI and POSTN. Deficiency of scavenger receptors Stabilin-1 and Stabilin-2 in mice leads to age-dependent renal and hepatic deposition of TGFBI and Periostin, resulting in glomerulofibrosis and reduced lifespan.
Synapse has enriched 8 closely related papers on similar clinical questions. Consider them for comparative context: