Olmesartan Attenuates Kidney Fibrosis in a Murine Model of Alport Syndrome by Suppressing Tubular Expression of TGFβ
Abstract
:1. Introduction
2. Results
2.1. Olmesartan Ameliorates Kidney Fibrosis in Col4a3–/– Mice
2.2. Preferential Upregulation of TGFβ in Tubulointerstitium in Col4a3–/– Mice is Attenuated by Olmesartan
2.3. Downregulation of ACE2 in Col4a3–/– Mice Is Counteracted by Olmesartan
2.4. Olmesartan Prevents Apoptosis and Inflammation in the Kidneys of Col4a3–/– Mice
2.5. Olmesartan Targets RAS-TGFβ Feedback Loop to Regulate HK-2 Cell Fibrosis
3. Discussion
4. Materials and Methods
4.1. Experimental Animals and Protocols
4.2. Serum and urine NGAL measurement by ELISA
4.3. Histology and Immunohistochemistry
4.4. Detection of Apoptosis with Tunel Staining
4.5. Cell Culture
4.6. Semi-quantitative Immunoblotting
4.7. Real-Time qPCR
4.8. Measurement of BP
4.9. Statistical Analyses
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
References
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WT | Col4a3–/– | Col4a3-/-+Olm | |
---|---|---|---|
Body weight (g) | 19.7 ± 2.6 | 20.0 ± 0.4 | 20.7 ± 1.0 |
Kidney weight (g) | 0.1 ± 0.0 | 0.1 ± 0.0 | 0.1 ± 0.0 |
Kidney weight / body weight (g/kg) | 7.6 ± 1.6 | 9.3 ± 0.3 | 8.3 ± 0.4 |
Urine creatinine (mg/dL) | 49.0 ± 10.5 | 21.2 ± 3.5 * | 9.1 ± 3.3 ## |
Urine albumin (μg/mL) | 7.2 ± 2.0 | 234.5 ± 32.5 * | 72.0 ± 45.1 # |
Urine albumin-to-creatinine ratio | 15.1 ± 4.4 | 1119.0 ± 188.5 ** | 426.3 ± 105.1 **,## |
Serum NGAL (ng/mL) | 77.2 ± 7.5 | 335.5 ± 126.1 * | 43.8 ± 6.4 # |
Urine NGAL (ng/mL) | 61.1 ± 3.8 | 848.8 ± 12.7 ** | 27.8 ± 2.8 ## |
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Suh, S.H.; Choi, H.S.; Kim, C.S.; Kim, I.J.; Ma, S.K.; Scholey, J.W.; Kim, S.W.; Bae, E.H. Olmesartan Attenuates Kidney Fibrosis in a Murine Model of Alport Syndrome by Suppressing Tubular Expression of TGFβ. Int. J. Mol. Sci. 2019, 20, 3843. https://doi.org/10.3390/ijms20153843
Suh SH, Choi HS, Kim CS, Kim IJ, Ma SK, Scholey JW, Kim SW, Bae EH. Olmesartan Attenuates Kidney Fibrosis in a Murine Model of Alport Syndrome by Suppressing Tubular Expression of TGFβ. International Journal of Molecular Sciences. 2019; 20(15):3843. https://doi.org/10.3390/ijms20153843
Chicago/Turabian StyleSuh, Sang Heon, Hong Sang Choi, Chang Seong Kim, In Jin Kim, Seong Kwon Ma, James W. Scholey, Soo Wan Kim, and Eun Hui Bae. 2019. "Olmesartan Attenuates Kidney Fibrosis in a Murine Model of Alport Syndrome by Suppressing Tubular Expression of TGFβ" International Journal of Molecular Sciences 20, no. 15: 3843. https://doi.org/10.3390/ijms20153843