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: SA-PO148

Meprin β Regulates Protein Kinase A-Mediated TGF-β Signaling in Ischemia/Reperfusion-Induced Kidney Injury

Session Information

  • AKI: Mechanisms - III
    November 04, 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

Ischemia/reperfusion (IR) is a leading cause of acute kidney injury (AKI) and is associated with high morbidity and mortality rates. Meprins, zinc metalloproteases have been implicated in the pathology of IR. Meprins are capable to proteolytically processing the catalytic subunit of protein kinase A (PKA-C) and several mediators of inflammation. The protein kinase A (PKA) signaling pathway plays an important role in renal fibrosis, promoting the production of transforming growth factor-β (TGF-β) and/or TGF-β-dependent molecules. The TGF-β signaling is involved in wound healing and tissue repair of injured kidneys. Activation of Smad2 and Smad3 is the major downstream event of the TGF-β signaling pathway. The objective of the current study was to determine how meprin β expression impacts PKA C-mediated TGF-β signaling in IR-induced kidney injury.

Methods

We used surgical procedures to achieve unilateral IR with contralateral nephrectomy in wild-type (WT) and meprin β knockout (βKO) mice. The mice were sacrificed at 96 h post-IR and kidney tissues obtained for analysis. Real-time PCR, and immunohistochemical staining, were used to evaluate the expression levels of PKA C and TGF-β. Statistical analysis utilized two way ANOVA.

Results

Real-time PCR data showed significant increases in mRNA levels of PKA C only in βKO kidneys after IR. In contrast, the mRNA levels for TGF-β were higher in both WT and βKO at 96 h post-IR Interestingly, the baseline mRNA levels for TGF-β were higher in meprin βKO mice. Immunohistochemical data showed significant increases in the levels of PKA C proteins in select kidney tubules of both genotypes after IR. Similarly, staining intensity for TGF-β were higher in select kidney tubules of both WT and meprin β deficient mice at 96 h IR. Immunofluorescence of kidney tissues with anti-meprin β, anti-PKA C and anti-TGF-β antibodies showed a positive correlation between meprin β expression and tubular PKA C and TGF-β levels in kidneys subjected to IR.

Conclusion

These findings suggest that meprin β regulates PKA C-mediated TGF-β signaling pathway in IR-induced kidney injury and provides new insights on the mechanisms underlying meprin β modulation of the pathophysiology of IR-induced renal injury.

Funding

  • Other NIH Support