All-trans retinoic acid and glycated albumin reciprocally influence their effects in human mesangial cells.
All-trans-retinoic acid (tRA) modulates in human mesangial cells (MC) antioxidant defenses, the expression of interleukin-1beta-induced vascular cell-adhesion molecule-1 (VCAM-1), cyclooxygenase-2 (COX-2), and the retinoic acid-receptor-beta (RAR-beta). The correlation of the serum levels of glycated hemoglobin A1c with tRA in type 2 diabetes mellitus patients led us to hypothesize that tRA and glycated albumin (GA), the main circulating glycated protein, might mutually interact in MC. We studied 1) the influence of tRA on GA effects in cultured MC: an assessment was made on how pre-incubation with tRA modified the effects of GA on intracellular oxidation and on the expression of mRNA and protein of COX-2 and VCAM-1; and 2) the influence of GA on tRA effects in MC: we studied how the induction of RARbeta expression by tRA was modified by GA.


RESULTS
GA dose-dependently increased intracellular oxidation and the expression of the molecules involved in leukocyte infiltration, namely COX-2 and VCAM-1 . Pre-incubation with tRA exacerbated GA effects by up to a three- to four-fold additional increase. In turn, induction by tRA of RAR-beta was fully inhibited by GA. Thus tRA and GA reciprocally influence their effects in MC. It is possible that this interaction may have a pathophysiological or pharmacological role in diabetic nephropathy.
Alique
Matilde
M
Departamento de Fisiología, Facultad de Medicina, Universidad de Alcalá (Alcalá de Henares, Madrid, Spain).
Moreno-Manzano
Victoria
V
Sepúlveda-Muñoz
Juan Carlos
JC
Reyes-Martín
Patricia
P
Parra-Cid
Trinidad
T
Calvino
Myriam
M
de Lucio-Cazana
Francisco Javier
FJ
D000970:Antineoplastic Agents / Q000494:pharmacology*; D015153:Blotting, Western / Q000379:methods; D051546:Cyclooxygenase 2; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005920:Glomerular Mesangium / Q000187:drug effects*; D017127:Glycation End Products, Advanced; D006801:Humans; D066298:In Vitro Techniques; D008565:Membrane Proteins; D011451:Prostaglandin-Endoperoxide Synthases / Q000187:drug effects; D012333:RNA, Messenger / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D012709:Serum Albumin / Q000494:pharmacology*; D018709:Statistics, Nonparametric; D014212:Tretinoin / Q000494:pharmacology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000187:drug effects; D000093423:Glycated Serum Albumin
D000970:Antineoplastic Agents; D017127:Glycation End Products, Advanced; D008565:Membrane Proteins; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D012709:Serum Albumin; D019010:Vascular Cell Adhesion Molecule-1; D014212:Tretinoin; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D000093423:Glycated Serum Albumin