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

Abstract: FR-PO741

APOM Deficiency Affects Kidney Function in an Experimental Mouse Model of Alport Syndrome

Session Information

Category: Glomerular Diseases

  • 1401 Glomerular Diseases: Mechanisms, including Podocyte Biology

Authors

  • Molina David, Judith T., University of Miami Miller School of Medicine, Miami, Florida, United States
  • Tolerico, Matthew, University of Miami Miller School of Medicine, Miami, Florida, United States
  • Kim, Jin Ju, University of Miami Miller School of Medicine, Miami, Florida, United States
  • Fontanella, Antonio Miguel, University of Miami Miller School of Medicine, Miami, Florida, United States
  • Carrazco, Arianna, University of Miami Miller School of Medicine, Miami, Florida, United States
  • Merscher, Sandra M., University of Miami Miller School of Medicine, Miami, Florida, United States
  • Fornoni, Alessia, University of Miami Miller School of Medicine, Miami, Florida, United States

Group or Team Name

  • Katz Family Div of Nephrology and Hypertension/Peggy and Harold Katz Family Drug Discovery Center.
Background

We have previously reported that glomerular APOM deficiency correlates with eGFR in patients with glomerular diseases enrolled in the Nephrotic Syndrome Study Network (NEPTUNE). However, little is known about the significance of APOM deficiency in kidney disease development and progression. With this study, we investigate if APOM deficiency occurs in Alport Syndrome (AS) and how ApoM deficiency may contribute to disease progression.
We first analyzed glomerular APOM expression in a mouse model of progressive renal disease associated with AS (Col4a3 KO mice) and in podocytes isolated from Col4a3 KO mice. We found reduced mRNA and protein expression of APOM in glomeruli and podocytes isolated from Col4a3 KO mice.

Methods

To investigate if APOM replenishment would improve renal function in this mouse model, we injected Col4a3 KO mice with human recombinant APOM (rhAPOM). Three groups of mice were studied, n=6 mice per group: (1) Col4a3 +/+ (WT) + vehicle, (2) Col4a3 -/- (KO) + vehicle, and (3) Col4a3 -/- (KO) + rhAPOM. rhAPOM was administered by weekly ip injection starting at 4 w of age and until sacrifice at 8 w of age.
APOM protein levels in podocytes were measured by Western blot analysis. Serum and urine samples were used to determine blood urea nitrogen (BUN), creatinine, and urinary albumin/creatinine ratios (ACR). Triglyceride content (TG) was assayed using a colorimetric kit and lipid droplets (LD) content was using the OPERA screening system. Histological analysis was performed by Periodic Acid Schiff (PAS), renal fibrosis was evaluated by Picro Sirius Red (PSR), renal lipid content was determined by Oil Red O (ORO) and WT1 to detect podocytes number.

Results

Glomerular APOM mRNA and protein expression were markedly reduced in Col4a3 KO mice when compared to WT mice. Treatment of Col4a3 KO podocytes with rhAPOM reduce TG levels and LD content and treatment of Col4a3 KO mice with rhAPOM normalized renal APOM levels and resulted in a significant reduction of serum BUN and creatinine levels, a reduced ACR.

Conclusion

rhAPOM treatment protected from the development of glomerulosclerosis and kidney fibrosis.