Decreased renal expression of PAQR5 is associated with the absence of a nephroprotective effect of progesterone in a rat UUO model
Abstract Fibrosis is a severe complication of chronic kidney disease (CKD). Progesterone, like other sex hormones, plays an important role in renal physiology, but its role in CKD is poorly understood. We investigated progesterone effect on renal fibrosis progression in the rat model of unilateral u...
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| Format: | Article |
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Nature Portfolio
2023-08-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-39848-2 |
| _version_ | 1827634946435448832 |
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| author | P. A. Abramicheva D. S. Semenovich L. D. Zorova I. B. Pevzner I. A. Sokolov V. A. Popkov E. P. Kazakov D. B. Zorov E. Y. Plotnikov |
| author_facet | P. A. Abramicheva D. S. Semenovich L. D. Zorova I. B. Pevzner I. A. Sokolov V. A. Popkov E. P. Kazakov D. B. Zorov E. Y. Plotnikov |
| author_sort | P. A. Abramicheva |
| collection | DOAJ |
| description | Abstract Fibrosis is a severe complication of chronic kidney disease (CKD). Progesterone, like other sex hormones, plays an important role in renal physiology, but its role in CKD is poorly understood. We investigated progesterone effect on renal fibrosis progression in the rat model of unilateral ureteral obstruction (UUO). Female rats were exposed to UUO, ovariectomy and progesterone administration after UUO with ovariectomy. Expression of key fibrosis markers, proinflammatory cytokines, levels of membrane-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, collagen deposition, and MMP2 activity in all UUO kidneys. Progesterone had slight or no effect on the change in these markers. Thus, we demonstrate for the first time diminished sensitivity of the kidney to progesterone associated with renal fibrosis due to a severe decrease in PAQR5 expression that was accompanied by the lack of nephroprotection in a rat UUO model. |
| first_indexed | 2024-03-09T15:20:26Z |
| format | Article |
| id | doaj.art-56ff668a9dcc4137b096530bc23134a7 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-09T15:20:26Z |
| publishDate | 2023-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-56ff668a9dcc4137b096530bc23134a72023-11-26T12:48:54ZengNature PortfolioScientific Reports2045-23222023-08-0113111210.1038/s41598-023-39848-2Decreased renal expression of PAQR5 is associated with the absence of a nephroprotective effect of progesterone in a rat UUO modelP. A. Abramicheva0D. S. Semenovich1L. D. Zorova2I. B. Pevzner3I. A. Sokolov4V. A. Popkov5E. P. Kazakov6D. B. Zorov7E. Y. Plotnikov8A.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State UniversityA.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State UniversityA.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State UniversityA.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State UniversityA.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State UniversityA.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State UniversityA.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State UniversityA.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State UniversityA.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State UniversityAbstract Fibrosis is a severe complication of chronic kidney disease (CKD). Progesterone, like other sex hormones, plays an important role in renal physiology, but its role in CKD is poorly understood. We investigated progesterone effect on renal fibrosis progression in the rat model of unilateral ureteral obstruction (UUO). Female rats were exposed to UUO, ovariectomy and progesterone administration after UUO with ovariectomy. Expression of key fibrosis markers, proinflammatory cytokines, levels of membrane-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, collagen deposition, and MMP2 activity in all UUO kidneys. Progesterone had slight or no effect on the change in these markers. Thus, we demonstrate for the first time diminished sensitivity of the kidney to progesterone associated with renal fibrosis due to a severe decrease in PAQR5 expression that was accompanied by the lack of nephroprotection in a rat UUO model.https://doi.org/10.1038/s41598-023-39848-2 |
| spellingShingle | P. A. Abramicheva D. S. Semenovich L. D. Zorova I. B. Pevzner I. A. Sokolov V. A. Popkov E. P. Kazakov D. B. Zorov E. Y. Plotnikov Decreased renal expression of PAQR5 is associated with the absence of a nephroprotective effect of progesterone in a rat UUO model Scientific Reports |
| title | Decreased renal expression of PAQR5 is associated with the absence of a nephroprotective effect of progesterone in a rat UUO model |
| title_full | Decreased renal expression of PAQR5 is associated with the absence of a nephroprotective effect of progesterone in a rat UUO model |
| title_fullStr | Decreased renal expression of PAQR5 is associated with the absence of a nephroprotective effect of progesterone in a rat UUO model |
| title_full_unstemmed | Decreased renal expression of PAQR5 is associated with the absence of a nephroprotective effect of progesterone in a rat UUO model |
| title_short | Decreased renal expression of PAQR5 is associated with the absence of a nephroprotective effect of progesterone in a rat UUO model |
| title_sort | decreased renal expression of paqr5 is associated with the absence of a nephroprotective effect of progesterone in a rat uuo model |
| url | https://doi.org/10.1038/s41598-023-39848-2 |
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