Collecting duct cells show differential retinoic acid responses to acute versus chronic kidney injury stimuli

Alexandros Papadimitriou, Paola Romagnani, Maria Lucia Angelotti, Mazhar Noor, Jonathan Corcoran, Katie Raby, Patricia D Wilson, Joan Li, Donald Fraser, Remi Piedagnel, Bruce Hendry, Qihe Xu

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

Abstract

Retinoic acid (RA) activates RA receptors (RAR), resulting in RA response element (RARE)-dependent gene expression in renal collecting duct (CD). Emerging evidence supports a protective role for this activity in acute kidney injury (AKI) and chronic kidney disease (CKD). Herein, we examined this activity in RARE-LacZ transgenic mice and by RARE-Luciferase reporter assays in CD cells, and investigated how this activity responds to neurotransmitters and mediators of kidney injury. In RARE-LacZ mice, Adriamycin-induced heavy albuminuria was associated with reduced RA/RAR activity in CD cells. In cultured CD cells, RA/RAR activity was repressed by acetylcholine, albumin, aldosterone, angiotensin II, high glucose, cisplatin and lipopolysaccharide, but was induced by aristolochic acid I, calcitonin gene-related peptide, endothelin-1, gentamicin, norepinephrine and vasopressin. Compared with age-matched normal human CD cells, CD-derived renal cystic epithelial cells from patients with autosomal recessive polycystic kidney disease (ARPKD) had significantly lower RA/RAR activity. Synthetic RAR agonist RA-568 was more potent than RA in rescuing RA/RAR activity repressed by albumin, high glucose, angiotensin II, aldosterone, cisplatin and lipopolysaccharide. Hence, RA/RAR in CD cells is a convergence point of regulation by neurotransmitters and mediators of kidney injury, and may be a novel therapeutic target.

Original languageEnglish
Article number16683
Number of pages12
JournalScientific Reports
Volume10
Issue number1
DOIs
Publication statusPublished - 1 Dec 2020

Fingerprint

Dive into the research topics of 'Collecting duct cells show differential retinoic acid responses to acute versus chronic kidney injury stimuli'. Together they form a unique fingerprint.

Cite this