Yishen Jiangzhuo Granules (益肾降浊冲剂) affect tubulointerstitial fibrosis via a mitochondrion-mediated apoptotic pathway

Yan-fang Xu; Shi-wei Ruan; Jiu-mao Lin; zheng Zhang

doi:10.1007/s11655-015-2078-5

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Yishen Jiangzhuo Granules (益肾降浊冲剂) affect tubulointerstitial fibrosis via a mitochondrion-mediated apoptotic pathway

OriginalPaper | Updated：2021-08-27

- Yishen Jiangzhuo Granules (益肾降浊冲剂) affect tubulointerstitial fibrosis via a mitochondrion-mediated apoptotic pathway
- Yishen Jiangzhuo Granules (益肾降浊冲剂) affect tubulointerstitial fibrosis via a mitochondrion-mediated apoptotic pathway
- 中国结合医学杂志（英文版） 2015年21卷第12期页码：928-937
- Affiliations：
  
  1. Department of Nephrology, The First Affiliated Hospital, Fujian Medical University,Fuzhou,China
  2. Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine,Fuzhou,China
  3. People Hospital Affiliated to Fujian University of Traditional Chinese Medicine,Fuzhou,China
- Author bio：
- Funds：
- DOI：10.1007/s11655-015-2078-5
  中图分类号：
- 纸质出版日期：2015，
  
  网络出版日期：2015-5-9，
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Xu, Yf., Ruan, Sw., Lin, Jm. et al. Yishen Jiangzhuo Granules (益肾降浊冲剂) affect tubulointerstitial fibrosis via a mitochondrion-mediated apoptotic pathway., Chin. J. Integr. Med. 21, 928–937 (2015). https://doi.org/10.1007/s11655-015-2078-5

Yan-fang Xu, Shi-wei Ruan, Jiu-mao Lin, et al. Yishen Jiangzhuo Granules (益肾降浊冲剂) affect tubulointerstitial fibrosis via a mitochondrion-mediated apoptotic pathway[J]. Chinese Journal of Integrative Medicine, 2015,21(12):928-937.
Xu, Yf., Ruan, Sw., Lin, Jm. et al. Yishen Jiangzhuo Granules (益肾降浊冲剂) affect tubulointerstitial fibrosis via a mitochondrion-mediated apoptotic pathway., Chin. J. Integr. Med. 21, 928–937 (2015). https://doi.org/10.1007/s11655-015-2078-5 DOI：

Yan-fang Xu, Shi-wei Ruan, Jiu-mao Lin, et al. Yishen Jiangzhuo Granules (益肾降浊冲剂) affect tubulointerstitial fibrosis via a mitochondrion-mediated apoptotic pathway[J]. Chinese Journal of Integrative Medicine, 2015,21(12):928-937. DOI： 10.1007/s11655-015-2078-5.

摘要

To investigate the effect of Yishen Jiangzhuo Granules (益肾降浊冲剂

YSJZG) on mitochondrial injury and regeneration and renal tubular epithelial cell apoptosis in chronic renal failure (CRF) rats and explore its mechanism from molecular pathology

gene

protein levels

and relative pathway. The CRF rat model was established using 5/6 nephrectomy. Sixty rats were randomly divided into six groups: sham-operation group

model (CRF) group

Niaoduqing Granules (尿毒清颗粒)-treated group [5 g/(kg.day)]

low-

moderate-

and high-dose [L-YSJZG

M-YSJZG

H-YSJZG at 3

and 9 g/(kg day)] YSJZG-treated group (n=10 each). The levels of serum creatinine (Scr)

blood urea nitrogen (BUN)

and 24-h urine protein were assessed after 10 weeks of treatment. The tubulointerstitial injury and collagen deposition were evaluated using periodic acid-schiff stain and Masson staining. Renal tubular epithelial cell apoptosis was assessed using the terminal deoxynucleotidyl transferase dUTP nick end labeling assay

mitochondrial injury was observed using an electron microscope

and superoxide dismutase (SOD)

glutathione (GSH) and malondialdehyde (MDA) levels were assessed using chromometry. Transforming growth factor-β1 (TGF-β1) expression was assessed using immunohistochemistry. The expressions of Bax

Bcl-2

peroxisome proliferator-activated receptor γ coactivator- 1α (PGC-1α)

mitochondrial transcription factor A (Tfam)

mitogen-activated protein kinases (MAPK) phosphorylation were evaluated by Western blot. YSJZG decreased the 24-h urine protein

BUN

Scr

remnant kidney weight-to-body weight ratio

renal tubular injury

deposition of collagen

and the apoptosis of renal tubular epithelial cells in a dose-dependent manner. YSJZG dose-dependently restored the number and structure of mitochondria and the expression of Tfam and PCG-1α

up-regulated the expression of Bcl-2

and inhibited the expression of Bax. YSJZG also dose-dependently inhibited TGF-β1 expression

increased SOD and GSH activity

decreased the MDA level

and inhibited p38MAPK and pERK1/2 phosphorylation (all P<0.01). YSJZG improved the renal function in rats with CRF and inhibited the progression of tubulointerstitial fibrosis by dose-dependently alleviating mitochondrial injury

restoring the expression of Tfam and PCG-1α

and inhibiting renal tubular epithelial cell apoptosis through inhibiting activation of reactive oxygen species-MAPK signaling.

Abstract

To investigate the effect of Yishen Jiangzhuo Granules (益肾降浊冲剂

YSJZG) on mitochondrial injury and regeneration and renal tubular epithelial cell apoptosis in chronic renal failure (CRF) rats and explore its mechanism from molecular pathology

gene

protein levels

and relative pathway. The CRF rat model was established using 5/6 nephrectomy. Sixty rats were randomly divided into six groups: sham-operation group

model (CRF) group

Niaoduqing Granules (尿毒清颗粒)-treated group [5 g/(kg.day)]

low-

moderate-

and high-dose [L-YSJZG

M-YSJZG

H-YSJZG at 3

and 9 g/(kg day)] YSJZG-treated group (n=10 each). The levels of serum creatinine (Scr)

blood urea nitrogen (BUN)

mitochondrial injury was observed using an electron microscope

and superoxide dismutase (SOD)

glutathione (GSH) and malondialdehyde (MDA) levels were assessed using chromometry. Transforming growth factor-β1 (TGF-β1) expression was assessed using immunohistochemistry. The expressions of Bax

Bcl-2

peroxisome proliferator-activated receptor γ coactivator- 1α (PGC-1α)

mitochondrial transcription factor A (Tfam)

mitogen-activated protein kinases (MAPK) phosphorylation were evaluated by Western blot. YSJZG decreased the 24-h urine protein

BUN

Scr

remnant kidney weight-to-body weight ratio

renal tubular injury

deposition of collagen

and the apoptosis of renal tubular epithelial cells in a dose-dependent manner. YSJZG dose-dependently restored the number and structure of mitochondria and the expression of Tfam and PCG-1α

up-regulated the expression of Bcl-2

and inhibited the expression of Bax. YSJZG also dose-dependently inhibited TGF-β1 expression

increased SOD and GSH activity

decreased the MDA level

restoring the expression of Tfam and PCG-1α

and inhibiting renal tubular epithelial cell apoptosis through inhibiting activation of reactive oxygen species-MAPK signaling.

关键词

Yishen Jiangzhuo Granulestubulointerstitial fibrosisapoptosismitochondriaoxidative stressmitogen-activated protein kinase signalingChinese Medicine

Keywords

Yishen Jiangzhuo Granulestubulointerstitial fibrosisapoptosismitochondriaoxidative stressmitogen-activated protein kinase signalingChinese Medicine

references

Sharma K, Cook A, Smith M, Valancius C, Inscho EW. TGF-β impairs renal autoregulation via generation of ROS. Am J Physiol Renal 2005;288: F1069–F1077.

Sun L, Xiao L, Nie J, Liu FY, Ling GH, Zhu XJ, et al. p66Shc mediates high-glucose and angiotensin II-induced oxidative stress renal tubular injury via mitochondrial-dependent apoptotic pathway. Am J Physiol Renal 2010;299: F1014–F1025.

Funk JA, Odejinmi S, Schnellmann RG. SRT1720 induces mitochondrial biogenesis and rescues mitochondrial function after oxidant injury in renal proximal tubule cells. J Pharmacol Exp Ther 2010;333:593–601.

Martin MM, Buckenberger JA, Jiang J, Malana GE, Knoell DL, Feldman DS, et al. TGF-β1 stimulates human AT1 receptor expression in lung fibroblasts by cross talk between the Smad, p38 MAPK, JNK, and PI3K signaling pathways. Am J Physiol Lung-C 2007;293:L790–L799.

Ventura-Clapier R, Garnier A, Veksler V. Transcriptional control of mitochondrial biogenesis: the central role of PGC-1a. Cardiovasc Res 2008;79:208–217.

Xu YF, Ruan SW, Zhang Z. Protective effect and mechanism of Yishenjiangzhuo Granules on renal glomerulosclerosis. China J Tradit Chin Med Pharm (Chin) 2011;26:2844–2848.

Kim K J, Moradi H, Yuan J, Norris K, Vaziri ND. Renal mass reduction results in accumulation of lipids and dysregulation of lipid regulatory proteins in the remnant kidney. Am J Physiol Renal Physiol 2009;296:F1297–F1306.

Xu YF, Ruan SW, Wan JX, Zhang Z. Effect of Yishenjiangzhuo Granules on accumulation of lipids and tubulointerstitial injury in remnant kidney of 5/6 nephrectomy rats. Chin J Integr Trad West Nephrol (Chin) 2011;12:852–855.

Xu Y, Ruan S, Xie H, Lin JM. Role of LOX-1 in Ang II-induced oxidative functional damage in renal tubular epithelial cells. Int J Mol Med 2010;26: 679–690.

Zeisberg M, Hanai J, Sugimoto H, Mammoto T, Charytan D, Strutz F, et al. BMP-7 counteracts TGF-beta1-induced epithelial to mesenchymal transition and reverses chronic renal injury. Nat Med 2003;9:964–968.

Rouschop KMA, Claessen N, Pals ST, Weening JJ, Florquin S. CD44 disruption prevents degeneration of the capillary network in obstructive nephropathy via reduction of TGF-β1-induced apoptosis. J Am Soc Nephrol 2006;17:746–753.

Doughan AK, Harrison DG, Dikalov SI. Molecular mechanisms of angiotensin II-mediated mitochondrial dysfunction linking mitochondrial oxidative damage and vascular endothelial dysfunction. Circ Res 2008; 102:488–496.

Rego AC, Oliveira CR. Mitochondrial dysfunction and reactive oxygen species in excitotoxicity and apoptosis: implications for the pathogenesis of neurodegenerative diseases. Neurochem Res 2003;28:1563–1574.

Rasbach KA, Schnellmann RG. Signaling of mitochondrial biogenesis following oxidant injury. J Biol Chem 2007;282:2355–2362.

Park CB, Larsson NG. Mitochondrial DNA mutations in disease and aging. J Cell Biol 2011;193:809–818.

Arany Z, He H, Lin J, Hoyer K, Handschin C, Toka O, et al. Transcriptional coactivator PGC-1 alpha controls the energy state and contractile function of cardiac muscle. Cell Metab 2005;1:259–271.

Adhihetty PJ, Taivassalo T, Haller RG, Walkinshaw DR, Hood DA. The effect of training on the expression of mitochondrial biogenesis-and apoptosis-related proteins in skeletal muscle of patients with mtDNA defects. Am J Physiol Endocrinol Metab 2007;293:E672–E680.

Ryan MT, Hoogenraad NJ. Mitochondrial-nuclear communications. Annu Rev Biochem 2007;76:701–722.

Arany I, Megyesi JK, Kaneto H, Tanaka S, Safirstein RL. Activation of ERK or inhibition of JNK ameliorates H(2)O(2) cytotoxicity in mouse renal proximal tubule cells. Kidney Int 2004;65:1231–1239.

Adhihetty PJ, Uguccioni G, Leick L, Hidalgo J, Pilegaard H, Hood DA. The role of PGC-1α on mitochondrial function and apoptotic susceptibility in muscle. Am J Physiol Cell Physiol 2009;297:C217–C225.

Valle I, Alvarez-Barriento A, Arza E, Lamas ST, Monsalve M. PGC-1α regulates the mitochondrial antioxidant defense system in vascular endothelial cells. Cardiovasc Res 2005;66:562–573.

Hu C, Dandapat A, Sun L, Khan JA, Liu Y, Hermonat PL, et al. Regulation of TGFbeta1-mediated collagen formation by LOX-1: studies based on forced overexpression of TGFbeta1 in wild-type and lox-1 knock-out mouse cardiac fibroblasts. J Biol Chem 2008;283:10226–10231.

Rhyu DY, Yang Y, Ha H, Lee GT, Song JS, Uh ST, et al. Role of reactive oxygen species in TGF-beta1-induced mitogen-activated protein kinase activation and epithelialmesenchymal transition in renal tubular epithelial cells. J Am Soc Nephrol 2005;16:667–675.

Lee EA, Seo JY, Jiang Z, Yu MR, Kwon MK, Ha H, et al. Reactive oxygen species mediate high glucose-induced plasminogen activator inhibitor-1 up-regulation in mesangial cells and in diabetic kidney. Kidney Int 2005;67:1762–1771.

Xu YF, Yang SY, Huang JY, Ruan SW, Zhang Z, Lin JM. TGF-β1 induced autophagy and promoted apoptosis in renal tubular epithelial cells. Int J Mol Med 2012;29:781–790.

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