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-PO168

Meprin β Activity Modulates Cellular Proliferation via Trans-Signaling IL-6-Mediated AKT/ERK Pathway in Ischemia/Reperfusion (IR)-Induced Kidney Injury 

Session Information

  • AKI: Mechanisms - II
    November 03, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
    Abstract Time: 10:00 AM - 12:00 PM

Category: Acute Kidney Injury

  • 103 AKI: Mechanisms

Authors

  • Abousaad, Shaymaa, North Carolina Agricultural and Technical State University, Greensboro, North Carolina, United States
  • Ahmed, Faihaa, NC State University, Raleigh, North Carolina, United States
  • Abouzeid, Ayman, North Carolina Agricultural and Technical State University, Greensboro, North Carolina, United States
  • Ongeri, Elimelda Moige, North Carolina Agricultural and Technical State University, Greensboro, North Carolina, United States
Background

Inflammation plays a central role in the progression of kidney injury induced by ischemia/reperfusion (IR). Meprin metalloproteinases have been implicated in the pathophysiology of IR-induced kidney injury. We previously showed that meprin β modulates cellular survival (BCL-2) through IL-6/JAK/STAT signaling pathway in IR-induced kidney injury. However, it’s not known how meprin β modulation of the IL-6 signaling pathway impacts the cellular proliferation in IR-induced AKI. IL-6 trans-signaling induces proliferation through either MAPK/ERK or PI3K/AKT pathway or in crosstalk with AKT/ERK. PCNA is a cellular proliferation marker that is induced through activation of the IL-6 signaling pathway. The goal of the current study was to determine how meprin β modulation of the IL-6 signaling pathway impacts downstream cellular proliferation in IR-induced kidney injury.

Methods

We used the unilateral IR as a model of renal inflammation in wild-type (WT) and meprin β knockout (βKO) male mice, with the contralateral kidneys serving as controls. The mice were sacrificed at 96 h post-IR, and kidney tissue processed for evaluation by RT-PCR and immunohistochemistry. Statistical analysis of data utilized two-way ANOVA.

Results

Our PCR data showed significant increase in mRNA levels for IL-6 and PCNA in WT and βKO mice at 96 h-post IR when compared to WT control kidneys. Immunohistochemical data showed significant increases in IL-6, PCNA, p-AKT and p-ERK in select tubules in both genotypes at 96 h post-IR compared to control kidneys. Data from immunofluorescence of kidney tissues showed that the levels of IL-6, PCNA, p-AKT and p-ERK were higher in meprin β-expressing proximal tubules (PTs), at 96 h post-IR when compared to the distal kidney tubules (DTs), which lack meprins. High levels of IL-6 were also present in the lumen of PTs and DTs from WT and βKO kidneys at 96 h post-IR, suggesting increased release into filtrate and subsequently into urine. However, high levels of PCNA, p-AKT and p-ERK were present in the lumen of PTs only from both genotypes at 96 h post-IR.

Conclusion

In conclusion, our data shows that meprin β activity modulates cellular proliferation via trans-signaling IL-6-mediated AKT/ERK pathway in IR-induced kidney injury.

Funding

  • Other NIH Support