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Abstract: TH-PO428

Interstitial LRP1 Expression Is Associated With Glomerular Disease

Session Information

Category: Glomerular Diseases

  • 1301 Glomerular Diseases: Fibrosis and Extracellular Matrix

Authors

  • Groener, Marwin, Yale School of Medicine, New Haven, United States
  • Jobst-Schwan, Tilman, Universitatsklinikum Erlangen Medizinische Klinik 4 Nephrologie und Hypertensiologie, Erlangen, Bayern, Germany
  • Schiffer, Mario, Universitatsklinikum Erlangen Medizinische Klinik 4 Nephrologie und Hypertensiologie, Erlangen, Bayern, Germany
Background

Low density lipoprotein receptor-related protein 1 (LRP1) is a large evolutionarily conserved endocytic transmembrane receptor that is ubiquitously expressed. However, little is known about its function in the kidney. The goal of this study was to investigate LRP1 expression in different nephron segments in healthy and diseased human renal tissue as well as the developing kidney.

Methods

Immunohistochemistry with two antibodies targeted towards the intracellular and extracellular domains of LRP1 were used to assess spatial distribution of LRP1 in healthy human renal tissue and in biopsies of minimal change disease, focal segmental glomerulosclerosis, and membranous nephropathy. Perinatal and adult mouse kidneys were assessed with immunohistochemistry for LRP1. Published kidney RNA and ATAC sequencing databases were used to evaluate LRP1 transcription levels in different renal cell types.

Results

In healthy human tissue, intracellular LRP1 signal was detected in distal tubules (DT), loop of Henle (LH), and collecting ducts (CD), whereas extracellular domain signal was found in proximal tubules (PT) and weaker in LH. No glomerular or interstitial signal was found with either antibody. Surprisingly, marked glomerular and interstitial LRP1 expression was seen in all glomerulopathies. Glomerular expression did not co-localize with nephrin and had a mesangial pattern. Interstitial LRP1 was pronounced in the peritubular space. In P0 mouse kidneys, LRP1 signal was primarily found in the interstitium and S-shaped body, whereas adult mouse tissue predominantly expressed LRP1 in the PT. RNA and ATAC sequencing database analysis indicated preferential transcription of LRP1 in mesangial cells and fibroblasts.

Conclusion

Interstitial LRP1 expression is markedly induced in human proteinuric glomerulopathies. Interestingly, the developing mouse kidney has similar interstitial LRP1 expression which is lost in mature renal tissue. Our findings demonstrate an association of interstitial LRP1 with glomerular disease and kidney development. Further research is needed to elucidate the role of LRP1 in renal disease and its potential as a drug target.

Funding

  • Private Foundation Support