Angiotensin (1-7) participating in renal fibrosis by inhibiting intermediate conductance Ca2+ -activated K+ channels protein expression

XU Shi LIU Yao-hao WANG Li-ping

Acta Anatomica Sinica ›› 2019, Vol. 50 ›› Issue (4) : 512-516.

PDF(5460 KB)
Welcome to visit Acta Anatomica Sinica! Today is Chinese
PDF(5460 KB)
Acta Anatomica Sinica ›› 2019, Vol. 50 ›› Issue (4) : 512-516. DOI: 10.16098/j.issn.0529-1356.2019.04.018
Histology,Embryology and Developmental Biology

Angiotensin (1-7) participating in renal fibrosis by inhibiting intermediate conductance Ca2+ -activated K+ channels protein expression

  •  XU Shi LIU Yao-hao WANG Li-ping*
Author information +
History +

Abstract

Objective To investigate the relationship between the protective effect of angiotensin (Ang) (1-7) and the protein expression of intermediate conductance Ca2+ -activated K+ channels (KCa3.1) in renal fibrosis. Methods Totally 60 male mice were randomly divided into 5 groups: control group (WT); Ang Ⅱ group: mice received Ang Ⅱ [1.4 mg/(kg.d)]by hypodermic injection; Ang Ⅱ blocker group (Losartan): mice received Ang Ⅱ [1.4 mg/(kg.d)]and Losartan [40 mg/(kg.d)]by hypodermic injection; Ang (1-7) group: mice received Ang Ⅱ [1.4 mg/(kg.d)]and Ang (1-7) [0.14 mg/(kg.d)]by hypodermic injection; diminazene aceturate(DIZE) group: mice received Ang Ⅱ [1.4 mg/(kg.d)]and DIZE [10 mg/(kg.d)]by hypodermic injection. After 4 weeks of continuous administration, the related indicators were detected. Masson staining was used to detect the collagen content, and Western blotting was used to detect the protein expression of collagen type Ⅰ, collagen type Ⅲ and KCa3.1 channel. Results Collagen deposition in renal tissue increased significantly after 4 weeks of hypodermic injection of Ang Ⅱ (n=12,P<0.01) compared with the WT group, which suggested that the model of renal fibrosis was successfully reproduced. Ang Ⅱ significantly increased the synthesis of collagen type Ⅰ and Ⅲ (n=6,P<0.01) and increased the expression of KCa3.1 channel protein (n=6,P<0.01) in renal tissues, while Ang (1-7) and ACE2 activator DIZE significantly inhibited those exchanges (n=12 or 6,P<0.01). Conclusion Ang (1-7) plays a protective role in the process of renal fibrosis, which may be related to the downregulation of KCa3.1 channel protein expression in renal tissue.

Key words

Fibrosis / Renal / Angiotensin (1-7) / Intermediate conductance Ca2+ activated K+ channel / Western blotting / Mouse

Cite this article

Download Citations
XU Shi LIU Yao-hao WANG Li-ping. Angiotensin (1-7) participating in renal fibrosis by inhibiting intermediate conductance Ca2+ -activated K+ channels protein expression[J]. Acta Anatomica Sinica. 2019, 50(4): 512-516 https://doi.org/10.16098/j.issn.0529-1356.2019.04.018

References

 [1] Feng Y, Hans C,Mcllwain E, et al. Over-expression in the central nervous system reduces angiotensin-Ⅱ-mediated cardiac hypertrophy[J]. PLoS One, 2012, 7(11):e48910.
 [2] Wang, Fan SJ, Li SM, et al. Protective role of ACE2-Ang-(1-7)-Mas in myocardial fibrosis by downregulating KCa 3.1 channel via ERK1/2 pathway[J]. Pflugers Arch, 2016, 468(11-12):2041-2051.
 [3] Eddy AA. Overview of the cellular and molecular basis of kidney fibrosis[J]. Kidney Int Suppl, 2014, 4(1): 2-8.
 [4] Mack M, Yanagita M. Origin of myofibroblasts and cellular events triggering fibrosis[J]. Kidney Int, 2015, 87(2):297-307. 
 [5] Boor, Floege J. The renal (myo-)fibroblast: A heterogeneous group of cells[J]. Nephrol Dial Transplant, 2012, 27(8):3027-3036.
 [6] Thieme, Sivritas SH, Mergia E, et al. Phosphodiesterase 5 inhibition ameliorates angiotensin Ⅱ-dependenthypertension and renal vascular dysfunction[J].Am J Physiol Renal Physiol, 2017,312(3): F474-F478.
 [7] Wen, Liu Y, Tang T, et al. NLRP3 inflammasome activation is involved in Ang Ⅱ-induced kidney damage via mitochondrial dysfunction[J].Oncotarget,  2016, 7(34):54290-54302.
 [8] Norlander, Saleh MA, Kamat NV, et al. Interleukin 17A regulates renal sodium transporters and renal injury in angiotensin Ⅱ-induced hypertension[J]. Hypertension, 2016, 68(1):167-174. 
 [9] Casare, Thieme K, Costa-Pessoa JM, et al. Renovascular remodeling and renal injury after extended angiotensin Ⅱ infusion[J].Am J Physiol Renal Physiol, 2016, 310(11): F1295-F1307.
 [10]Liu Y, Sun XJ, Li Ch, et al. Advances in the roles of microRNA-29 in renal fibrosis[J].Acta Anatomica Sinica,2017,48(5): 622-627.  (in Chinese)
刘祎,孙雪娇,李城, 等.MicroRNA-29在肾纤维化进程中的研究进展[J].解剖学报,2017,48(5): 622-627.
 [11] Liu Z, Huang XR, Lan HY. Smad3 mediates ANG Ⅱ-induced hypertensive kidney disease in mice[J]. Am J Physiol Renal Physiol, 2012, 302(8):F986-997.
 [12] Rüster R, Wolf G. Angiotensin Ⅱ as a morphogenic cytokine stimulating renal fibrogenesis[J]. J Am Soc Nephrol, 2011, 22(7):1189-1199. 
 [13] Yan FN, Liu SX, Cui L, et al. Effect of TRPV4 on angiotensin Ⅱ-induced renal injury in mice[J]. Chinese Journal of Comparative Medicine, 2018, 28(2):1-6. (in Chinese)
闫凤娜,刘素晓,崔琳, 等.TRPV4受体对血管紧张素Ⅱ诱导的小鼠肾损害的影响[J].中国比较医学杂志, 2018, 28(2):1-6. 
 [14] Mu?oz MC, Burghi Ⅴ, Miquet JG, et al. Downregulation of the ACE2/Ang-(1-7)/Mas axis in transgenic mice overexpressing GH [J]. J Endocrinol, 2014, 221(2):215-227.
 [15] Fu, Zhang T, Wang L,et al. Inhibition of the K(+)channel KCa3.1 reduces TGF-β1-induced premature senescence, myofibroblast phenotype transition and proliferation of mesangial cells[J]. PLoS One, 2014, 9(1):e87410.
 [16] Giani JF, Miquet JG, Muoz MC, et al. Upregulation of the angiotensin-converting enzyme 2/angiotensin-(1-7)/Mas receptor axis in the heart and the kidney of growth hormone receptor knock-out mice[J]. Growth Horm IGF Res, 2012, 22(6):224-233.
 [17] Chen CL, Liao JW, Hu OY, et al. Blockade of KCa-3.1 potassium channels protects against cisplatin-induced acute kidney injury[J].Arch Toxicol, 2016, 90(9):2249-2260. 
 [18] Guimar?es GG, Santos SH, Oliveira ML, et al. Exercise induces renin-angiotensin system unbalance and high collagen expression in the heart of Mas-deficient mice[J]. Peptides, 2012, 38(1):54-61.
 [19] Huang C, Zhang L, Shi Y, et al. The KCa 3.1 blocker TRAM34 reverses renal damage in a mouse model of established diabetic nephropathy[J]. PLoS One, 2018, 13(2):e0192800. 
PDF(5460 KB)

Accesses

Citation

Detail

Sections
Recommended

/