Abstract

Cyclooxygenase-2 Increases Its Expression by Recruitment of Neighboring Epithelial Cells from the Thick Ascending Limb of Henle Carlos P. Vio,1 Natalia A. Mendez,1,2 Carlos Cespedes.1 1Center for Aging and Regeneration, Dept Physiology, Ponti cia Univ Catolica de Chile, Santiago, Chile; 2Inst Anatomy, Histology and Pathology, Univ Austral de Chile, Valdivia, Chile. Background: Cyclooxygenase-2 (COX-2) is an enzyme that contributes to regulation of renal function via local prostaglandins. We described its origin in a subset of cells from the thick ascending limb of Henle (TALc). COX-2 is regulated in physiological conditions by dietary sodium, glucocorticoids, postnatal development and a negative feedback loop mediated by PGE2 EP3 receptor. COX-2 increases its expression along the axis of the TAL segment and we hypothesize that this follows a recruitment pattern. Methods: We used renal tissue from a wide variety of conditions, some are new experiments such as SD adult rats with adrenalectomy (ADX), or treated with coxibs (rofecoxib), or with ACEi (ramipril), or AT1 blockers (ARBs, losartan), or EP3 antagonist (L-798106). Other tissue was obtained from our collection of stored tissue: microdissected nephrons from treated rats, or early postnatal ages (5 to 15 days). The tissue was stained by immunohistochemistry, the levels of the enzyme quanti ed by its protein by Western blot and mRNA by RT-qPCR. Results: A wide variety of stimuli produced the same pattern of recruitment of epithelial cells from TAL, with highest levels during early postnatal age, lowest levels in adult, and increased in ADX, ACEi, ARBs or EP3 antagonist. This axial recruitment was con rmed in microdissected nephrons. Conclusions: Regardless of the stimuli, when COX-2 increases, a recruitment phenomenon was observed. The recruitment phenomenon is rare, and the most studied is a similar recruitment observed with renin expression in the afferent arteriole. Both COX-2 and renin recruitment share similarities like regulation by sodium, postnatal development, ACEi and ARBs. Funding Fondecyt 1130741, CONICYT PIA/Basal PFB12, SQM. Funding: Government Support - Non-U.S.