Summary- paper 43:
Novel Mechanism for Tubular Injury in Nephropathic Cystinosis
Swastika Sur, Maggie Kerwin, Silvia Pineda, Poonam Sansanwal, Tara K. Sigdel, Marina Sirota, Minnie M. Sarwal
Biorxiv, 2022
Questions/gaps addressed:
- Cystinosis is a rare autosomal recessive LSD, caused by mutations in the CTNS gene. The kidney is the first organ affected functionally. The most severe form is nephropathic/infantile cystinosis, resulting in end-stage renal disease (ESRD) by 10 years of age. What is the mechanism of defects in renual tubular cells, are these due to functions besides cystine transport?
Major hypothesis:
- Defective lysosomal clearance may be a pivotal cause of the altered function of renal proximal tubular epithelial cells (RPTECs).
Key methods:
- whole-genome microarray transcriptional expression profiles in RPTECs (isolated from patient urine samples) and fibroblasts (isolated from the same patient skin biopsies) from patients with cystinosis and healthy age- and gender-matched controls.
Major takeaways:
- vATPase subunits levels are affected in CTNS KO