Transmembrane protein 14A protects glomerular filtration barrier integrity

Author:

Khalil Ramzi1ORCID,Bonnemaijer Josephine D. D.1ORCID,Kreutz Reinhold2ORCID,Spaink Herman P.3ORCID,Hogendoorn Pancras C. W.1ORCID,Baelde Hans J.1ORCID

Affiliation:

1. Department of Pathology Leiden University Medical Center Leiden The Netherlands

2. Institute of Clinical Pharmacology and Toxicology Charité ‐ University Medicine Berlin Germany

3. Institute of Biology Leiden Leiden University Leiden The Netherlands

Abstract

AbstractTransmembrane protein 14A (TMEM14A) is a relatively unknown protein that is now identified to be required for maintaining the integrity of the glomerular filtration barrier. It is an integral transmembrane protein of 99 amino acids with three transmembrane domains. TMEM14A has been implied to suppress Bax‐mediated apoptosis in other studies. Other than that, little is currently known of its function. Here, we show that its expression is diminished before onset of proteinuria in a spontaneously proteinuric rat model. Knocking down tmem14a mRNA translation results in proteinuria in zebrafish embryos without affecting tubular reabsorption. Also, it is primarily expressed by podocytes. Lastly, an increase in glomerular TMEM14A expression is exhibited in various proteinuric renal diseases. Overall, these results suggest that TMEM14A is a novel factor in the protective mechanisms of the nephron to maintain glomerular filtration barrier integrity.

Funder

Nierstichting

Publisher

Wiley

Subject

Physiology (medical),Physiology

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