Effect of zinc on high glucose-induced epithelial-to-mesenchymal transition in renal tubular epithelial cells

Zhang, Xiuli; Liang, Dan; Chen, Zhihong; Chu, Qingqing; Zhao, Chenghai; Ma, Rongzheng; Zhao, Yue; Li, Hongjuan

doi:10.3892/ijmm.2015.2170

Cited by 32 publications

(30 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Hence it often acts as a mesenchymal marker in renal fibrosis [34]. As shown in Figure 5b,c, the reduction of E-ca protein expression in HG conditions was accompanied by an increase of α-SMA protein expression, which was close associated with our preliminary experiments, and confirmed that HG promotes EMT development in NRK-52E cells [35]. However, HG-induced EMT was decreased after pre-treating the NRK-52E cells with BBR, these demonstrated that BBR could reduce α-SMA and E-ca expression together.…”

Section: Resultssupporting

confidence: 79%

“…A previous study demonstrates that BBR treatment may be related with AMPK pathway together with Nrf2 pathway may lead to the increase of NQO1 and HO-1 in both LPS-shocked macrophages and mice, and that means AMPK is a upstream of Nrf2 [52]. In addition, BBR can induce the activation of PI3K/Akt and p38 pathway, which both can upregulate the expression and activity of HO-1 as well as NQO1 [35]. Moreover, other studies have revealed that BBR as an Nrf2 activator against glucose neurotoxicity so that attenuating high glucose-induced neurotoxicity, these findings provided another potential therapeutic use of BBR on the treatment of diabetic complications [27].…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Protective Effects of Berberine on Renal Injury in Streptozotocin (STZ)-Induced Diabetic Mice

Zhang

He²,

Liang³

et al. 2016

IJMS

Self Cite

View full text Add to dashboard Cite

Diabetic nephropathy (DN) is a serious diabetic complication with renal hypertrophy and expansion of extracellular matrices in renal fibrosis. Epithelial-to-mesenchymal transition (EMT) of renal tubular epithelial cells may be involved in the main mechanism. Berberine (BBR) has been shown to have antifibrotic effects in liver, kidney and lung. However, the mechanism of cytoprotective effects of BBR in DN is still unclear. In this study, we investigated the curative effects of BBR on tubulointerstitial fibrosis in streptozotocin (STZ)-induced diabetic mice and the high glucose (HG)-induced EMT in NRK 52E cells. We found that BBR treatment attenuated renal fibrosis by activating the nuclear factor-erythroid 2-related factor 2 (Nrf2) signaling pathway in the diabetic kidneys. Further revealed that BBR abrogated HG-induced EMT and oxidative stress in relation not only with the activation of Nrf2 and two Nrf2-targeted antioxidative genes (NQO-1 and HO-1), but also with the suppressing the activation of TGF-β/Smad signaling pathway. Importantly, knockdown Nrf2 with siRNA not only abolished the BBR-induced expression of HO-1 and NQO-1 but also removed the inhibitory effect of BBR on HG-induced activation of TGF-β/Smad signaling as well as the anti-fibrosis effects. The data from present study suggest that BBR can ameliorate tubulointerstitial fibrosis in DN by activating Nrf2 pathway and inhibiting TGF-β/Smad/EMT signaling activity.

show abstract

Section: Resultssupporting

confidence: 79%

Section: Discussionmentioning

confidence: 99%

Protective Effects of Berberine on Renal Injury in Streptozotocin (STZ)-Induced Diabetic Mice

Zhang

He²,

Liang³

et al. 2016

IJMS

Self Cite

View full text Add to dashboard Cite

show abstract

“…Although the exact role of EMT in renal fibrosis remains to be established [24], it is widely believed that renal tubular EMT is one of the critical factors mediating RIF. Oxidative stress damage is associated with the pathogenesis of RIF by tubular EMT [25]. …”

Section: Discussionmentioning

confidence: 99%

GSTA3 Attenuates Renal Interstitial Fibrosis by Inhibiting TGF-Beta-Induced Tubular Epithelial-Mesenchymal Transition and Fibronectin Expression

Xiao

Liu

et al. 2016

PLoS ONE

View full text Add to dashboard Cite

Tubular epithelial-mesenchymal transition (EMT) has been widely accepted as the underlying mechanisms of renal interstitial fibrosis (RIF). The production of reactive oxygen species (ROS) plays a vital role in tubular EMT process. The purpose of this study was to investigate the involved molecular mechanisms in TGF-beta-induced EMT and identify the potential role of glutathione S-transferase alpha 3 (GSTA3) in this process. The iTRAQ screening was performed to identify protein alterations of the rats underwent unilateral-ureteral obstruction (UUO). Protein expression of GSTA3 in patients with obstructive nephropathy and UUO rats was detected by immunohistochemistry. Protein and mRNA expression of GSTA3 in UUO rats and NRK-52E cells were determined by Western blot and RT-PCR. siRNA and overexpression plasmid were transfected specifically to assess the role of GSTA3 in RIF. The generation of ROS was measured by dichlorofluorescein fluorescence analysis. GSTA3 protein and mRNA expression was significantly reduced in UUO rats. Immunohistochemical analysis revealed that GSTA3 expression was reduced in renal cortex in UUO rats and patients with obstructive nephropathy. Treating with TGF-β1 down-regulated GSTA3 expression in NRK-52E cells, which have been found to be correlated with the decreased expression in E-cadherin and megalin and increased expression in α-smooth muscle actin. Furthermore, knocking down GSTA3 in NRK-52 cells led to increased production of ROS and tubular EMT, whereas overexpressing GSTA3 ameliorated ROS production and prevented the occurrence of tubular EMT. GSTA3 plays a protective role against tubular EMT in renal fibrosis, suggesting GSTA3 is a potential therapeutic target for RIF.

show abstract

“…Consistent with this, we found that in the absence of ZnT4, Akt expression was much lower in the lactating mammary gland. Accumulation of intracellular Zn decreases Akt expression (53), and the inability to mobilize Zn pools from the Golgi apparatus may also reduce Akt signaling (47). Whether reduced Akt expression in C57BL/6J lm/lm mice was a direct effect of dysregulated Zn homeostasis in the Golgi apparatus, global defects in Golgi organization and signaling scaffolds (35), ZnT2-mediated Zn accumulation into vesicles withholding Zn from activating Akt phosphorylation, or further alterations in cellular Zn homeostasis, is not currently understood.…”

Section: Ck8mentioning

confidence: 99%

ZnT4 (SLC30A4)-null (“lethal milk”) mice have defects in mammary gland secretion and hallmarks of precocious involution during lactation

McCormick

Lee

Hennigar

et al. 2016

American Journal of Physiology-Regulatory, Integrative and Comp

View full text Add to dashboard Cite

McCormick NH, Lee S, Hennigar SR, Kelleher SL. ZnT4 (SLC30A4)-null ("lethal milk") mice have defects in mammary gland secretion and hallmarks of precocious involution during lactation. Am J Physiol Regul Integr Comp Physiol 310: R33-R40, 2016. First published November 4, 2015 doi:10.1152/ajpregu.00315.2014.-During lactation, highly specialized secretory mammary epithelial cells (MECs) produce and secrete huge quantities of nutrients and nonnutritive factors into breast milk. The zinc (Zn) transporter ZnT4 (SLC30A4) transports Zn into the trans-Golgi apparatus for lactose synthesis, and across the apical cell membrane for efflux from MECs into milk. This is consistent with observations in "lethal milk" (lm/lm) mice, which have a truncation mutation in SLC30A4, and present with not only low milk Zn concentration, but also smaller mammary glands, decreased milk volume, and lactation failure by lactation day 2. However, the molecular underpinnings of these defects are not understood. Here, we used lactating C57BL/6J lm/lm (ZnT4-null) mice to explore the consequences of a ZnT4-null phenotype on mammary gland function during early lactation. Lactating C57BL/6J lm/lm mice had significantly fewer, smaller, and collapsed alveoli comprising swollen, lipid-filled MECs during early lactation. These defects were associated with decreased Akt expression and STAT5 activation, indicative of defects in MEC secretion. In addition, increased expression of ZnT2, TNF-␣, and cleaved e-cadherin concomitant with increased activation of STAT3 implicated the loss of ZnT4 in precocious activation of involution. Collectively, our study indicates that the loss of ZnT4 has profound consequences on MEC secretion and may promote tissue remodeling in the mammary gland during early lactation.zinc; lactation; mammary gland; SLC30A4; ZnT4 ZNT4 (SLC30A4) IS A ZINC (Zn) transporter that is expressed in numerous tissues, including the liver (13), lung (13), small intestine (28), and mammary gland (13). ZnT4 is particularly important for mammary gland function, as ZnT4 expression increases dramatically during lactation (23). Previous studies in vitro established that ZnT4 transports Zn into the transGolgi apparatus of the mammary epithelial cell (MEC) and delivers Zn to critical Zn-dependent proteins, including galactosyltransferase (a resident Golgi protein that is vital for lactose production) and carbonic anhydrase VI (a secreted milk enzyme that is vital for infant alimentary tract pH balance) (15). The "lethal milk" mouse (C57BL/6J lm/lm ) carries a spontaneous truncation mutation in SLC30A4, resulting in non-sense-mediated decay of ZnT4 mRNA (29). During lactation, ZnT4-null mice have ϳ35% lower milk Zn concentration than their wild-type littermates (37). Although this implicates ZnT4 in Zn secretion into milk, studies in breastfeeding women have yet to identify defects in ZnT4 in women with low milk Zn levels or find an association with transient neonatal Zn deficiency in exclusively breastfed infants (4,14,20). Moreover, ZnT4-null mice have s...

show abstract

Effect of zinc on high glucose-induced epithelial-to-mesenchymal transition in renal tubular epithelial cells

Cited by 32 publications

References 48 publications

Protective Effects of Berberine on Renal Injury in Streptozotocin (STZ)-Induced Diabetic Mice

Protective Effects of Berberine on Renal Injury in Streptozotocin (STZ)-Induced Diabetic Mice

GSTA3 Attenuates Renal Interstitial Fibrosis by Inhibiting TGF-Beta-Induced Tubular Epithelial-Mesenchymal Transition and Fibronectin Expression

ZnT4 (SLC30A4)-null (“lethal milk”) mice have defects in mammary gland secretion and hallmarks of precocious involution during lactation

Contact Info

Product

Resources

About