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: TH-PO1111

Emx2 Regulates Ciliogenesis by Controlling Prostaglandin Production

Session Information

  • CKD: Mechanisms - 1
    October 24, 2024 | Location: Exhibit Hall, Convention Center
    Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

  • 2303 CKD (Non-Dialysis): Mechanisms

Authors

  • Nguyen, Thanh Khoa, University of Notre Dame, Notre Dame, Indiana, United States
  • Wingert, Rebecca A., University of Notre Dame, Notre Dame, Indiana, United States
Background

Cilia serve important homeostasis roles in fluid flow and sensing to maintain a healthy kidney, and cilia defects have been linked to chronic kidney diseases. Renal multiciliated cells (MCCs) are an aberrant ciliated cell type found in several human kidney pathological states.

Methods

Here, we hypothesized empty spiracles homeobox gene 2 (emx2) is important for cilia development in monociliated cells and MCCs. Utilizing several emx2 deficient models, we performed in situ hybridization, renal clearance assays and immunohistochemistry to assess cilia development and function. We studied the relationship between emx2 and known regulators of the prostaglandin biosynthesis in the kidney such as ppargc1a, its downstream targets ptgs1 and the prostaglandin molecule PGE2 through a series of qualitative, quantitative and rescue experiments. Finally, we assessed renal basal body functions and performed rescue experiments with PGE2 in emx2 deficient models.

Results

We discovered that emx2 is expressed across ciliated tissues, such as the otic vesicle, nasal placode and renal MCCs. Our emx2 deficient models displayed reduced cilia development in nephrons, Kupffer’s vesicle, neuromasts and the ear. Furthermore, emx2 deficient embryos displayed a significant reduction in the number of renal MCCs and kidney functional defects including delayed renal clearance, which was associated with pericardial edema. Interestingly, emx2 deficiency reduced ppargc1a and ptgs1 expression, and the provision of transcripts encoding ppargc1a or ptgs1, or the supplement of endogenous PGE2, was sufficient to partially rescue cilia length, intensity and number of ciliated basal bodies. Lastly, we discovered that emx2 deficiency led to aberrantly positioned basal bodies in the nephron tubule epithelium, which was successfully rescued with PGE2.

Conclusion

Taken together, our study revealed that emx2 is an essential regulator of cilia development across tissues through the modulation of prostaglandin biosynthesis.