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Cited by 154Chronic Kidney Disease and DiabetesRenal Diseases and GlomerulopathiesLiver physiology and pathology

Deficiency of liver sinusoidal scavenger receptors stabilin-1 and -2 in mice causes glomerulofibrotic nephropathy via impaired hepatic clearance of noxious blood factors

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Schledzewski, Kai, Géraud, Cyrill, Arnold, Bernd, Wang, Shijun, Gröne, Hermann-Josef, Kempf, Tibor, Wollert, Kai C., Straub, Beate K. +8 more·2011·Journal of Clinical Investigation
DOI 10.1172/jci44740PMC PMC3026735
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Abstract

Tissue homeostasis and remodeling are processes that involve high turnover of biological macromolecules. Many of the waste molecules that are by-products or degradation intermediates of biological macromolecule turnover enter the circulation and are subsequently cleared by liver sinusoidal endothelial cells (LSEC). Besides the mannose receptor, stabilin-1 and stabilin-2 are the major scavenger receptors expressed by LSEC. To more clearly elucidate the functions of stabilin-1 and -2, we have generated mice lacking stabilin-1, stabilin-2, or both stabilin-1 and -2 (Stab1–/– Stab2–/– mice). Mice lacking either stabilin-1 or stabilin-2 were phenotypically normal; however, Stab1–/– Stab2–/– mice exhibited premature mortality and developed severe glomerular fibrosis, while the liver showed only mild perisinusoidal fibrosis without dysfunction. Upon kidney transplantation into WT mice, progression of glomerular fibrosis was halted, indicating the presence of profibrotic factors in the circulation of Stab1–/– Stab2–/– mice. While plasma levels of known profibrotic cytokines were unaltered, clearance of the TGF-β family member growth differentiation factor 15 (GDF-15) was markedly impaired in Stab1–/– Stab2–/– mice but not in either Stab1–/– or Stab2–/– mice, indicating that it is a common ligand of both stabilin-1 and stabilin-2. These data lead us to conclude that stabilin-1 and -2 together guarantee proper hepatic clearance of potentially noxious agents in the blood and maintain tissue homeostasis not only in the liver but also distant organs.

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  • STAB1 and STAB2 are located on different chromosomes (3 and 12), but both encode related scavenger receptors expressed on macrophages and liver sinusoidal endothelial cells that mediate the clearance of aged plasma proteins and other waste molecules.

    “STAB1 and STAB2 are located on different chromosomes (3 and 12, respectively), but both encode related scavenger receptors expressed on macrophages and liver sinusoidal endothelial cells that mediate the clearance of aged plasma proteins and other waste molecules21,22.”

    From Rare variant associations with plasma protein levels in the UK Biobank (2023) · cites this paper as [21]

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Authors
Schledzewski, K., Géraud, C., Arnold, B., Wang, S., Gröne, H.-J., Kempf, T., Wollert, K. C., Straub, B. K., Schirmacher, P., Demory, A., Schönhaber, H., Gratchev, A., Dietz, L., Thierse, H.-J., Kzhyshkowska, J., & Goerdt, S.
Affiliations
  • Heidelberg University (DE)
  • German Cancer Research Center (DE)
  • Medizinische Hochschule Hannover (DE)
Corresponding author
Géraud, Cyrill
ORCID
Venue
Journal of Clinical Investigation
Publisher
American Society for Clinical Investigation
Published
2011-02-01
Volume
121
Issue
2
Pages
703-714
ISSN
0021-9738 (ISSN-L)
DOI
10.1172/jci44740
PMC
PMC3026735
OpenAlex
W2166644552
Cited by
154
References
1
Citations by year
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FWCI
5.96
Type
journal article
Language
en
Open access
Locations
  • Journal of Clinical Investigation (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Deutsche Forschungsgemeinschaft (GRK880, SFB405, Project B1, SFB‐TR23)
  • Nederlandse Organisatie voor Wetenschappelijk Onderzoek
Topics
  • Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
  • Health Sciences › Medicine › Nephrology › Renal Diseases and Glomerulopathies
  • Health Sciences › Medicine › Hepatology › Liver physiology and pathology
Keywords
stabilin-1, stabilin-2, liver sinusoidal endothelial cells, scavenger receptors, hepatic clearance, growth differentiation factor 15, TGF-beta superfamily, profibrotic factors, tissue homeostasis, liver fibrosis, kidney transplantation
MeSH terms
Animals, Humans, Kidney, Kidney Diseases, Liver, Mice, Inbred BALB C, Mice, Inbred C57BL, Toxins, Biological, Cell Adhesion Molecules, Neuronal, Survival Rate, Transforming Growth Factor beta, Mice, Knockout, Collagen Type III, Mice

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