Premium
Proliferation of Macula Densa cells in Response to Succinate
Author(s) -
Blebu Bridgette E,
Toma Ildiko,
Vargas Sarah L,
Koo Jahoo J,
PetiPeterdi Janos
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.981.2
Subject(s) - macula densa , cell growth , chemistry , mapk/erk pathway , endocrinology , diabetic nephropathy , kidney , medicine , biology , renin–angiotensin system , signal transduction , biochemistry , blood pressure
The kidney normally functions under the stress of hypoxia, but when coupled with diabetes mellitus, the altered metabolism in the citric acid cycle leads to robust accumulation of intra‐renal succinate. Succinate is the ligand for the newly identified metabolic receptor GPR91 that signals through MAPK Erk1/2 and p38 in macula densa cells (MD), a special cell type in the kidney which controls renal blood flow, glomerular filtration and the renin‐angiotensin system. The MAPK system is well‐established to trigger cell proliferation and also involved in diabetic nephropathy. Here we aimed to study whether succinate via GPR91 causes MD cell proliferation and altered MD signaling. Mouse macula densa‐derived cells (MMDD1) were grown to 70% confluency and treated with succinate (10 uM, 100 uM and 1 mM) for 24‐hrs, followed by treatment with a fluorogenic proliferation assay reagent. Succinate caused a dose‐dependent proliferation of MMDD1 cells with a peak 2.6‐fold increase in cell number at 1 mM. There was increased MD COX‐2 expression in the STZ‐diabetic kidney which was GPR91‐dependent. Our new findings suggest a link between MD GPR91 expression and cell proliferation, MAPK and COX‐2 signaling in diabetes.