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Differential compensation of two cyclooxygenases in renal homeostasis is independent of prostaglandin-synthetic capacity under basal conditions
- Source :
- FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 32(10)
- Publication Year :
- 2018
-
Abstract
- The distinct functions of each cyclooxygenase (COX) isoform in renal homeostasis have been the subject of intense investigation for many years. We took the novel approach of using 3 characterized mouse lines, where the prostaglandin (PG)-endoperoxide synthase genes 1 and 2 ( Ptgs1 and Ptgs2) substitute for one another to delineate distinct roles and the potential for COX isoform substitution. Flipped Ptgs genes generate a reversed COX-expression pattern in the kidney, where the knockin COX-2 is highly expressed. Normal nephrogenesis was sustained in all 3 strains at the postnatal stage d 8 (P8). Knockin COX-1 can temporally restore renal function and delay but not prevent renal pathology consequent to COX-2 deletion. Loss of COX-2 in adult COX-1 > COX-2 mice results in severe nephropathy, which leads to impaired renal function. These defects are partially rescued by the knockin COX-2 in Reversa mice, whereas COX-2 can compensate for the loss of COX-1 in COX-2 > COX-1 mice. Intriguingly, the highly expressed knockin COX-2 enzyme barely makes any PGs or thromboxane in neonatal P8 or adult mice, demonstrating that prostanoid biosynthesis requires native COX-1 and cannot be rescued by the knockin COX-2. In summary, the 2 COX isoforms can preferentially compensate for some renal functions, which appears to be independent of the PG-synthetic capacity.-Li, X., Mazaleuskaya, L. L., Ballantyne, L. L., Meng, H., FitzGerald, G. A., Funk, C. D. Differential compensation of two cyclooxygenases in renal homeostasis is independent of prostaglandin-synthetic capacity under basal conditions.
- Subjects :
- 0301 basic medicine
Gene isoform
PTGS1
Kidney development
Prostaglandin
030204 cardiovascular system & hematology
Kidney
Biochemistry
03 medical and health sciences
chemistry.chemical_compound
Mice
0302 clinical medicine
Genetics
medicine
Animals
Gene Knock-In Techniques
Molecular Biology
biology
Research
Membrane Proteins
Mice, Mutant Strains
Cell biology
030104 developmental biology
medicine.anatomical_structure
Renal pathology
chemistry
Cyclooxygenase 2
biology.protein
Cyclooxygenase 1
Prostaglandins
Cyclooxygenase
Homeostasis
Biotechnology
Subjects
Details
- ISSN :
- 15306860
- Volume :
- 32
- Issue :
- 10
- Database :
- OpenAIRE
- Journal :
- FASEB journal : official publication of the Federation of American Societies for Experimental Biology
- Accession number :
- edsair.doi.dedup.....95b1edc3e0290a6a60e55e9334d3130b