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Angiotensin-(1-7) Attenuates Kidney Injury Due to Obstructive Nephropathy in Rats.
PLoS One. 2015; 10(11):e0142664.Plos

Abstract

BACKGROUND

Angiotensin-(1-7) [Ang-(1-7)] counteracts many actions of the renin-angiotensin-aldosterone system. Despite its renoprotective effects, extensive controversy exists regarding the role of Ang-(1-7) in obstructive nephropathy, which is characterized by renal tubulointerstitial fibrosis and apoptosis.

METHODS

To examine the effects of Ang-(1-7) in unilateral ureteral obstruction (UUO), male Sprague-Dawley rats were divided into three groups: control, UUO, and Ang-(1-7)-treated UUO rats. Ang-(1-7) was continuously infused (24 μg/[kg·h]) using osmotic pumps. We also treated NRK-52E cells in vitro with Ang II (1 μM) in the presence or absence of Ang-(1-7) (1 μM), Mas receptor antagonist A779 (1 μM), and Mas receptor siRNA (50 nM) to examine the effects of Ang-(1-7) treatment on Ang II-stimulated renal injury via Mas receptor.

RESULTS

Angiotensin II (Ang II) and angiotensin type 1 receptor (AT1R) protein expression was higher in UUO kidneys than in controls. Ang-(1-7) treatment also decreased proapoptotic protein expression in UUO kidneys. Ang-(1-7) also significantly ameliorated TUNEL positive cells in UUO kidneys. Additionally, Ang-(1-7) reduced profibrotic protein expression and decreased the increased tumor growth factor (TGF)-β1/Smad signaling present in UUO kidneys. In NRK-52E cells, Ang II induced the expression of TGF-β1/Smad signaling effectors and proapoptotic and fibrotic proteins, as well as cell cycle arrest, which were attenuated by Ang-(1-7) pretreatment. However, treatment with A779 and Mas receptor siRNA enhanced Ang II-induced apoptosis and fibrosis. Moreover, Ang II increased tumor necrosis factor-α converting enzyme (TACE) and decreased angiotensin-converting enzyme 2 (ACE2) expression in NRK-52E cells, while pretreatment with Ang-(1-7) or A779 significantly inhibited or enhanced these effects, respectively.

CONCLUSION

Ang-(1-7) prevents obstructive nephropathy by suppressing renal apoptosis and fibrosis, possibly by regulating TGF-β1/Smad signaling and cell cycle arrest via suppression of AT1R expression. In addition, Ang-(1-7) increased and decreased ACE2 and TACE expression, respectively, which could potentially mediate a positive feedback mechanism via the Mas receptor.

Authors+Show Affiliations

Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea.Department of Physiology, Chonnam National University Medical School, Gwangju, Korea.Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea.Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea.Department of Physiology, Chonnam National University Medical School, Gwangju, Korea.Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26556707

Citation

Kim, Chang Seong, et al. "Angiotensin-(1-7) Attenuates Kidney Injury Due to Obstructive Nephropathy in Rats." PloS One, vol. 10, no. 11, 2015, pp. e0142664.
Kim CS, Kim IJ, Bae EH, et al. Angiotensin-(1-7) Attenuates Kidney Injury Due to Obstructive Nephropathy in Rats. PLoS One. 2015;10(11):e0142664.
Kim, C. S., Kim, I. J., Bae, E. H., Ma, S. K., Lee, J., & Kim, S. W. (2015). Angiotensin-(1-7) Attenuates Kidney Injury Due to Obstructive Nephropathy in Rats. PloS One, 10(11), e0142664. https://doi.org/10.1371/journal.pone.0142664
Kim CS, et al. Angiotensin-(1-7) Attenuates Kidney Injury Due to Obstructive Nephropathy in Rats. PLoS One. 2015;10(11):e0142664. PubMed PMID: 26556707.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Angiotensin-(1-7) Attenuates Kidney Injury Due to Obstructive Nephropathy in Rats. AU - Kim,Chang Seong, AU - Kim,In Jin, AU - Bae,Eun Hui, AU - Ma,Seong Kwon, AU - Lee,JongUn, AU - Kim,Soo Wan, Y1 - 2015/11/10/ PY - 2015/06/19/received PY - 2015/10/26/accepted PY - 2015/11/12/entrez PY - 2015/11/12/pubmed PY - 2016/6/17/medline SP - e0142664 EP - e0142664 JF - PloS one JO - PLoS One VL - 10 IS - 11 N2 - BACKGROUND: Angiotensin-(1-7) [Ang-(1-7)] counteracts many actions of the renin-angiotensin-aldosterone system. Despite its renoprotective effects, extensive controversy exists regarding the role of Ang-(1-7) in obstructive nephropathy, which is characterized by renal tubulointerstitial fibrosis and apoptosis. METHODS: To examine the effects of Ang-(1-7) in unilateral ureteral obstruction (UUO), male Sprague-Dawley rats were divided into three groups: control, UUO, and Ang-(1-7)-treated UUO rats. Ang-(1-7) was continuously infused (24 μg/[kg·h]) using osmotic pumps. We also treated NRK-52E cells in vitro with Ang II (1 μM) in the presence or absence of Ang-(1-7) (1 μM), Mas receptor antagonist A779 (1 μM), and Mas receptor siRNA (50 nM) to examine the effects of Ang-(1-7) treatment on Ang II-stimulated renal injury via Mas receptor. RESULTS: Angiotensin II (Ang II) and angiotensin type 1 receptor (AT1R) protein expression was higher in UUO kidneys than in controls. Ang-(1-7) treatment also decreased proapoptotic protein expression in UUO kidneys. Ang-(1-7) also significantly ameliorated TUNEL positive cells in UUO kidneys. Additionally, Ang-(1-7) reduced profibrotic protein expression and decreased the increased tumor growth factor (TGF)-β1/Smad signaling present in UUO kidneys. In NRK-52E cells, Ang II induced the expression of TGF-β1/Smad signaling effectors and proapoptotic and fibrotic proteins, as well as cell cycle arrest, which were attenuated by Ang-(1-7) pretreatment. However, treatment with A779 and Mas receptor siRNA enhanced Ang II-induced apoptosis and fibrosis. Moreover, Ang II increased tumor necrosis factor-α converting enzyme (TACE) and decreased angiotensin-converting enzyme 2 (ACE2) expression in NRK-52E cells, while pretreatment with Ang-(1-7) or A779 significantly inhibited or enhanced these effects, respectively. CONCLUSION: Ang-(1-7) prevents obstructive nephropathy by suppressing renal apoptosis and fibrosis, possibly by regulating TGF-β1/Smad signaling and cell cycle arrest via suppression of AT1R expression. In addition, Ang-(1-7) increased and decreased ACE2 and TACE expression, respectively, which could potentially mediate a positive feedback mechanism via the Mas receptor. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/26556707/Angiotensin__1_7__Attenuates_Kidney_Injury_Due_to_Obstructive_Nephropathy_in_Rats_ L2 - https://dx.plos.org/10.1371/journal.pone.0142664 DB - PRIME DP - Unbound Medicine ER -