Tongluo Yishen Decoction Ameliorates Renal Fibrosis via Regulating Mitochondrial Dysfunction Induced by Oxidative Stress in Unilateral Ureteral Obstruction Rats

Tongluo Yishen (TLYS) decoction is an herb that is extensively applied for the treatment of chronic kidney disease (CKD) in traditional Chinese medicine. In this study, 37 different dominant chemical constituents of TLYS were identified. Rats with unilateral ureteral obstruction (UUO) were used as animal models, and TLYS decoction was administered orally for 14 days. TLYS decoction reduced the levels of renal function indicators, serum creatinine levels and blood urea nitrogen levels and alleviated renal pathological changes. Gene Ontology (GO) and KEGG pathway analyses of RNA sequencing data showed that TLYS decoction had significant effects on biological processes, cellular components and molecular functions in UUO rats and that the phagosome (a membrane source in the early stages of autophagy), lysosome (an important component of autolysosome), and oxidation pathways (which contribute to mitochondrial function) might be related to the antifibrotic effects of TLYS decoction. Moreover, we found significant mitochondrial function impairment, including a decreased mitochondrial membrane potential (MMP) and an imbalance in mitochondrial dynamics, excessive oxidative stress, and activation of Pink1/Parkin-mediated mitophagy in UUO rats. Treatment with TLYS decoction significantly increased the MMP, normalized mitochondrial dynamics and ameliorated renal injury. Moreover, TLYS alleviated the mitophagy clearance deficiency. In conclusion, our study showed that TLYS decoction can ameliorate mitochondrial dynamics by reducing oxidative stress and regulating mitophagy, thereby relieving renal injury, protecting renal function, and reducing renal fibrosis. This study provides support for the application of and further research on TLYS decoction.

Download Full-text

Sirtuin 3 Activation by Honokiol Decreases Unilateral Ureteral Obstruction-Induced Renal Inflammation and Fibrosis via Regulation of Mitochondrial Dynamics and the Renal NF-κB-TGF-β1/Smad Signaling Pathway

International Journal of Molecular Sciences ◽

10.3390/ijms21020402 ◽

2020 ◽

Vol 21 (2) ◽

pp. 402 ◽

Cited By ~ 4

Author(s):

Yi Quan ◽

Woong Park ◽

Jixiu Jin ◽

Won Kim ◽

Sung Kwang Park ◽

...

Keyword(s):

Signaling Pathway ◽

Ureteral Obstruction ◽

Renal Fibrosis ◽

Mitochondrial Dynamics ◽

Unilateral Ureteral Obstruction ◽

Sirtuin 3 ◽

Smad Signaling ◽

Renal Tubulointerstitial Fibrosis ◽

Smad Signaling Pathway ◽

Tgf Β1

Renal fibrosis is a common feature of all progressive chronic kidney diseases. Sirtuin 3 (SIRT3) is one of the mitochondrial sirtuins, and plays a role in the regulation of mitochondrial biogenesis, oxidative stress, fatty acid metabolism, and aging. Recently, honokiol (HKL), as a pharmaceutical SIRT3 activator, has been observed to have a protective effect against pressure overload-induced cardiac hypertrophy by increasing SIRT3 activity. In this study, we investigated whether HKL, as a SIRT3 activator, also has protective effects against unilateral ureteral obstruction (UUO)-induced renal tubulointerstitial fibrosis through SIRT3-dependent regulation of mitochondrial dynamics and the nuclear factor-κB (NF-κB)/transforming growth factor-β1 (TGF-β1)/Smad signaling pathway. We found that HKL decreased the UUO-induced increase in tubular injury and extracellular matrix (ECM) deposition in mice. HKL also decreased myofibroblast activation and proliferation in UUO kidneys and NRK-49F cells. Finally, we showed that HKL treatment decreased UUO-induced mitochondrial fission and promoted mitochondrial fusion through SIRT3-dependent effects. In conclusion, activation of SIRT3 via HKL treatment might have beneficial effects on UUO-induced renal fibrosis through SIRT3-dependent regulation of mitochondrial dynamics and the NF-κB/TGF-β1/Smad signaling pathway.

Download Full-text

Telmisartan inhibits both oxidative stress and renal fibrosis after unilateral ureteral obstruction in acatalasemic mice

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfi045 ◽

2005 ◽

Vol 20 (12) ◽

pp. 2670-2680 ◽

Cited By ~ 62

Author(s):

Hitoshi Sugiyama ◽

Mizuho Kobayashi ◽

Da-Hong Wang ◽

Reiko Sunami ◽

Yohei Maeshima ◽

...

Keyword(s):

Oxidative Stress ◽

Ureteral Obstruction ◽

Renal Fibrosis ◽

Unilateral Ureteral Obstruction

Download Full-text

KS‐370G ameliorates renal fibrosis, oxidative stress and inflammation induced by unilateral ureteral obstruction

The FASEB Journal ◽

10.1096/fasebj.26.1_supplement.1051.12 ◽

2012 ◽

Vol 26 (S1) ◽

Author(s):

Sung-Ting Chuang ◽

Ming-Jai Su

Keyword(s):

Oxidative Stress ◽

Ureteral Obstruction ◽

Renal Fibrosis ◽

Unilateral Ureteral Obstruction

Download Full-text

Chronic kidney disease induced in mice by reversible unilateral ureteral obstruction is dependent on genetic background

AJP Renal Physiology ◽

10.1152/ajprenal.00384.2009 ◽

2010 ◽

Vol 298 (4) ◽

pp. F1024-F1032 ◽

Cited By ~ 41

Author(s):

Tipu S. Puri ◽

Mohammed I. Shakaib ◽

Anthony Chang ◽

Liby Mathew ◽

Oladunni Olayinka ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Kidney Disease ◽

Renal Injury ◽

Ureteral Obstruction ◽

Genetic Background ◽

Renal Fibrosis ◽

Genetic Basis ◽

Cellular Responses ◽

Unilateral Ureteral Obstruction ◽

Number Of Factors

Chronic kidney disease (CKD) begins with renal injury; the progression thereafter depends upon a number of factors, including genetic background. Unilateral ureteral obstruction (UUO) is a well-described model of renal fibrosis and as such is considered a model of CKD. We used an improved reversible unilateral ureteral obstruction (rUUO) model in mice to study the strain dependence of development of CKD after obstruction-mediated injury. C57BL/6 mice developed CKD after reversal of three or more days of ureteral obstruction as assessed by blood urea nitrogen (BUN) measurements (>40 mg/dl). In contrast, BALB/c mice were resistant to CKD with up to 10 days ureteral obstruction. During rUUO, C57BL/6 mice exhibited pronounced inflammatory and intrinsic proliferative cellular responses, disruption of renal architecture, and ultimately fibrosis. By comparison, BALB/c mice had more controlled and measured extrinsic and intrinsic responses to injury with a return to normal within several weeks after release of ureteral obstruction. Our findings provide a model that allows investigation of the genetic basis of events during recovery from injury that contribute to the development of CKD.

Download Full-text