Involvement of matrix metalloproteinase-2 in the development of renal interstitial fibrosis in mouse obstructive nephropathy

Du, Xiang; Shimizu, Akira; Masuda, Yuki; Kuwahara, Naomi; Arai, Takashi; Kataoka, Mitue; Uchiyama, Masaaki; Kaneko, Takeshi; Akimoto, Toshio; Iino, Yuichi; Fukuda, Yuh

doi:10.1038/labinvest.2012.68

Cited by 93 publications

(70 citation statements)

References 47 publications

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“…Vehicle group. (Du et al, 2012). It is conceivable that the compensatory mechanisms are activated in response to the severe ECM protein deposition that probably influences MMP-9 protein expression detected in early stage of this renal failure model.…”

Section: Discussionmentioning

confidence: 94%

Ureic clearance granule, alleviates renal dysfunction and tubulointerstitial fibrosis by promoting extracellular matrix degradation in renal failure rats, compared with enalapril

Huang

Wei

Wan

et al. 2014

Journal of Ethnopharmacology

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Section: Discussionmentioning

confidence: 94%

Ureic clearance granule, alleviates renal dysfunction and tubulointerstitial fibrosis by promoting extracellular matrix degradation in renal failure rats, compared with enalapril

Huang

Wei

Wan

et al. 2014

Journal of Ethnopharmacology

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“…The expression of E-cadherin can also inhibit β-nuclear transcription [31]. MMPs could promote EMT progress by direct inhibition of E-cadherin expression [32,33,34,35]. Interestingly, most of the target genes in the Wnt/β-catenin signaling pathway, e.g., Snail, Twist, LEF1, and Jagged1, could also work as regulators or transcription factors of EMT.…”

Section: Discussionmentioning

confidence: 99%

Astragaloside IV Inhibits the Up-Regulation of Wnt/β-Catenin Signaling in Rats with Unilateral Ureteral Obstruction

Wang¹,

Chi²,

Yuan³

et al. 2014

Cell Physiol Biochem

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Objective: To investigate the effect of Astragaloside IV (AS-IV) on the regulation of the Wnt/β-catenin signaling pathway in rats with unilateral ureteral obstruction (UUO). Methods: Rat renal interstitial fibrosis models were prepared using unilateral ureteral ligation. Rats were randomly divided into sham group, sham group with AS-IV (33mg/kg), unilateral ureteral obstruction group, and unilateral ureteral obstruction group receiving varied doses of AS-IV (3.3, 10, and 33 mg/kg). Immunohistochemical analysis, real-time fluorescence quantitative PCR (FQ-PCR), and western blot were used to detect the expression of genes and proteins associated with the Wnt/β-catenin signaling pathway in renal tissues. Results: Levels of Wnt3, Wnt4, and Frizzled gene expression increased significantly in the UUO model; AS-IV was associated with the downregulation of the expression of Wnt3, Wnt4, Frizzled4, p-LRP5, p-LRP6, disheveled, β-catenin, LEF-1, TCF-1, Snail, Jagged 1, Twist, MMP2, and MMP7 proteins in a concentration-dependent manner, while the expression of APC, CK1, and E-cadherin was increased. Conclusions: AS-IV effectively inhibits the up-regulation of proteins in the Wnt/β-catenin signaling pathway in UUO-model rats, indicating its possible inhibitory effects on renal interstitial fibrosis.

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“…Histopathologically, RIF is characterized by distinct tubulointerstitial changes, including interstitial cell infiltration, tubular degeneration, increased number of myofibroblasts, oxidative stress, and accumulation of profibrotic factors and extracellular matrix (ECM) components. 8,9 Prohibitins (PHB) are ubiquitously expressed in a variety of cell types and multiple cellular compartments, including the mitochondria, nucleus, and the plasma membrane. 10 The family includes prohibitin 1 (PHB1) and prohibitin 2 (PHB2), and several other multifunctional intracellular proteins, which all play important roles in the regulation of cellular proliferation, apoptosis and differentiation.…”

Section: Introductionmentioning

confidence: 99%

Effect of all-trans retinoic acid treatment on prohibitin and renin–angiotensin–aldosterone system expression in hypoxia-induced renal tubular epithelial cell injury

Zhou

Liang

et al. 2014

J Renin Angiotensin Aldosterone Syst

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Background and objective: All-trans retinoic acid (ATRA) exerts various effects on physiological processes such as cell growth, differentiation, apoptosis and inflammation. Prohibitins (PHB), including prohibitin 1 (PHB1) and prohibitin 2 (PHB2), are evolutionary conserved and pleiotropic proteins implicated in various cellular functions, including proliferation, tumor suppression, apoptosis, transcription, and mitochondrial protein folding. The renin-angiotensinaldosterone system plays a pivotal role in the regulation of blood pressure and volume homeostasis. All these factors and systems have been implicated in renal interstitial fibrosis. Therefore, the objective of this study was to investigate the effect of ATRA treatment on the renin-angiotensin-aldosterone system and expression of prohibitins to further understand its role in the processes leading to renal interstitial fibrosis. Methods: The hypoxic and oxidative stress conditions in obstructive renal disease were simulated in a hypoxia/ reoxygenation model with renal tubular epithelial cells (RTEC) as a model system. Subsequently, the effect of ATRA on mRNA and protein expression levels was determined and correlations were established between factors involved in the renin-angiotensin-aldosterone system, the prohibitins, cellular redox status, renal interstitial fibrosis and ATRA treatment. Results: Correlation analysis showed that both PHB1 and PHB2 protein levels were negatively correlated with angiotensin I, ACE1, angiotensin II, TGF-β1, Col-IV, FN, ROS,; each p < 0.05), but positively correlated with ACE2, SOD, and GSH (PHB1: r = 0.796, 0.879, 0.824; PHB2: r = 0.785, 0.914, 0.849; each p < 0.05). ACE1 was positively correlated with angiotensin I, angiotensin II, TGF-β1, Col-IV, FN, ROS, and MDA, and negatively correlated with ACE2, SOD, and GSH (each p < 0.05). ACE2 was negatively correlated with ACE1, angiotensin I, angiotensin II, TGF-β1, Col-IV, FN, ROS, and MDA, and positively correlated with SOD and GSH (each p < 0.05). Conclusion:The results suggest that ATRA acts as a positive regulator of PHB1, PHB2 and ACE2, and as a negative regulator of ACE1, angiotensin I, and angiotensin II in a RTEC model system under hypoxia/reoxygenation conditions.

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Involvement of matrix metalloproteinase-2 in the development of renal interstitial fibrosis in mouse obstructive nephropathy

Cited by 93 publications

References 47 publications

Ureic clearance granule, alleviates renal dysfunction and tubulointerstitial fibrosis by promoting extracellular matrix degradation in renal failure rats, compared with enalapril

Ureic clearance granule, alleviates renal dysfunction and tubulointerstitial fibrosis by promoting extracellular matrix degradation in renal failure rats, compared with enalapril

Astragaloside IV Inhibits the Up-Regulation of Wnt/β-Catenin Signaling in Rats with Unilateral Ureteral Obstruction

Effect of all-trans retinoic acid treatment on prohibitin and renin–angiotensin–aldosterone system expression in hypoxia-induced renal tubular epithelial cell injury

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