Kidney Week

Abstract: TH-PO191

Transmembrane Protein 184A (TMEM184a) Expression in Rat Medullary Thick Ascending Limbs

Session Information

• Hypertension and CVD: Basic Research Findings
  October 24, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Hypertension and CVD

• 1601 Hypertension and CVD: Basic

Authors

• Jadhav, Darshan, Case Western Reserve University School of Medicine, Cleveland, Ohio, United States

Darshan Jadhav

• Forester, Beau, Case Western Reserve University School of Medicine, Cleveland, Ohio, United States

Beau Forester, MS

• Kim, Najeong, Case Western Reserve University School of Medicine, Cleveland, Ohio, United States

Najeong Kim, MS

• Garvin, Jeffrey L., Case Western Reserve University School of Medicine, Cleveland, Ohio, United States

Jeffrey L. Garvin, PhD

• Gonzalez-Vicente, Agustin, Case Western Reserve University School of Medicine, Cleveland, Ohio, United States

Agustin Gonzalez-Vicente, PhD

Group or Team Name

• Kidney Precision Medicine Project (KPMP).

Background

Nitric oxide production by NOS3 in thick ascending limbs (TAL) is essential for proper kidney function. TMEM184A is a heparin receptor found in endothelial cells that mediates NOS3 phosphorylation. The kidneys express TMEM184A, but its localization in nephron segments expressing NOS3 remains unclear. The Kidney Precision Medicine Project (KPMP) single cell (sc) and single nuclei RNA sequencing (RNAseq) transcriptomes show TMEM184A expression in proximal tubules and inner medullary collecting ducts, but not in TALs. On the contrary, KPMP’s regional transcriptomes show that TMEM184A is significantly overexpressed in the TAL (Δfc0.7; p≤0.05) as compared to other regions. The expression of Tmem184a in published rodent transcriptomes is similarly in dispute. The same laboratory reported that mouse medullary TAL had stronger TMEM184A mRNA expression than any nephron segment, while expression in rat medullary TAL was undetectable.

Methods

Consequently, we measured TMEM184A protein and mRNA expression by Western blot and scRNAseq in the outer medulla from Sprague Dawley rats.

Results

We found that the rat outer medulla expressed both, monomers and dimers of TMEM184A (Figure 1). Additionally, TMEM184A mRNA was significantly overexpressed in medullary TALs (Δfc1.7 p-Adj≤4x10^-18) when compared to other outer medullary epithelial cells types, i.e. proximal tubule S3 cells and the collecting duct principal and intercalated cells (Figure 2).

Conclusion

These data show that the rat medullary TAL express TMEM184A where it may play a role in NO production by NOS3 as it does in endothelial cells.

Funding

• NIDDK Support