Decreased renal expression of PAQR5 is associated with the absence of a nephroprotective effect of progesterone in a rat UUO model

Abramicheva, P.A.; Semenovich, D.S.; Zorova, L.D.; Pevzner, I.B.; Sokolov, I.A.; Popkov, V.A.; Kazakov, E.P.; Zorov, D.B.; Plotnikov, E.Y.

Авторы: Abramicheva P.A., Semenovich D.S., Zorova L.D., Pevzner I.B., Sokolov I.A., Popkov V.A., Kazakov E.P., Zorov D.B., Plotnikov E.Y.
Журнал: Scientific reports
Том: 13
Номер: 1
Год издания: 2023
Издательство: Nature Publishing Group
Местоположение издательства: United Kingdom
Номер статьи: 12871
DOI: 10.1038/s41598-023-39848-2
Аннотация: Fibrosis is a severe complication of chronic kidney disease (CKD). Progesterone, like other sexhormones, plays an important role in renal physiology, but its role in CKD is poorly understood. Weinvestigated progesterone effect on renal fibrosis progression in the rat model of unilateral ureteralobstruction (UUO). Female rats were exposed to UUO, ovariectomy and progesterone administrationafter UUO with ovariectomy. Expression of key fibrosis markers, proinflammatory cytokines, levels ofmembrane-bound (PAQR5) and nuclear (PGR) progesterone receptors, and matrix metalloproteinase(MMP) activity were analyzed in the obstructed and intact rat kidney. In all groups exposed to UUO,decreased PAQR5 expression was observed in the obstructed kidney while in the contralateral kidney,it remained unaffected. We found increased mRNA levels for profibrotic COL1A1, FN1, MMP2, TIMP1,TIMP2, proinflammatory IL1α, IL1β, and IL18, as well as elevated α-SMA and MMP9 proteins, collagendeposition, and MMP2 activity in all UUO kidneys. Progesterone had slight or no effect on the changein these markers. Thus, we demonstrate for the first time diminished sensitivity of the kidney toprogesterone associated with renal fibrosis due to a severe decrease in PAQR5 expression that wasaccompanied by the lack of nephroprotection in a rat UUO model
Добавил в систему: Абрамичева Полина Александровна

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Decreased renal expression of PAQR5 is associated with the absence of a nephroprotective effect of progesterone in a rat UUO modelстатья Исследовательская статья

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