ASN's Mission

To create a world without kidney diseases, the ASN Alliance for Kidney Health elevates care by educating and informing, driving breakthroughs and innovation, and advocating for policies that create transformative changes in kidney medicine throughout the world.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on X

Kidney Week

Please note that you are viewing an archived section from 2020 and some content may be unavailable. To unlock all content for 2020, please visit the archives.

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