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Kidney Week

Abstract: PO0610

Fibroblast-Specific LRP-1 Promotes Renal Fibrosis

Session Information

  • CKD Mechanisms - 1
    October 22, 2020 | Location: On-Demand
    Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

  • 2103 CKD (Non-Dialysis): Mechanisms

Authors

  • Lin, Ling, Penn State University College of Medicine, Hershey, Pennsylvania, United States
  • Hu, Kebin, Penn State University College of Medicine, Hershey, Pennsylvania, United States
Background

LRP-1, a scavenger receptor up-regulated during obstructive nephropathy, has been shown to mediate the actions of multiple profibrotic factors including tPA, TGF-β1, and CTGF. However, the in vivo role of LRP-1 in kidney fibrosis remains largely unknown.

Methods

We generated a novel fibroblast-specific LRP-1 knockout mouse (LRP-1-/-) and induced the unilateral ureteral obstruction (UUO), a classic model of chronic kidney disease (CKD), in these mice to investigate the in vivo role of LRP-1 in kidney fibrosis.

Results

It was found that LRP-1-/- mice had similar phenotype as their littermate controls (LRP-1+/+). However, after UUO injury, LRP-1-/- mice displayed significantly decreased fibrosis, as demonstrated by reduced renal collagen content and FSP-1 abundance, in comparison with their littermates. We further found that obstruction-induced epithelial damage was alleviated in LRP-1-/- mice. After UUO, LRP-1+/+ mice displayed decreased E-cadherin and increased vimentin expression, suggesting that epithelial-to-mesenchymal transition (EMT) was induced in the obstructed kidneys. Intriguingly, LRP-1-/- mice showed significantly reduced EMT as demonstrated by restoration of E-cadherin and elimination of vimentin induction.

Conclusion


Thus, it is clear that fibroblast LRP-1 promotes kidney fibrosis through EMT.

Funding

  • NIDDK Support