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Featured researches published by Zhongmin Tian.


Genome Research | 2008

MicroRNA–target pairs in the rat kidney identified by microRNA microarray, proteomic, and bioinformatic analysis

Zhongmin Tian; Andrew S. Greene; Jennifer L. Pietrusz; Isaac R. Matus; Mingyu Liang

Mammalian genomes contain several hundred highly conserved genes encoding microRNAs. In silico analysis has predicted that a typical microRNA may regulate the expression of hundreds of target genes, suggesting miRNAs might have broad biological significance. A major challenge is to obtain experimental evidence for predicted microRNA-target pairs. We reasoned that reciprocal expression of a microRNA and a predicted target within a physiological context would support the presence and relevance of a microRNA-target pair. We used microRNA microarray and proteomic techniques to analyze the cortex and the medulla of rat kidneys. Of the 377 microRNAs analyzed, we identified 6 as enriched in the renal cortex and 11 in the renal medulla. From approximately 2100 detectable protein spots in two-dimensional gels, we identified 58 proteins as more abundant in the renal cortex and 72 in the renal medulla. The differential expression of several microRNAs and proteins was verified by real-time PCR and Western blot analyses, respectively. Several pairs of reciprocally expressed microRNAs and proteins were predicted to be microRNA-target pairs by TargetScan, PicTar, or miRanda. Seven pairs were predicted by two algorithms and two pairs by all three algorithms. The identification of reciprocal expression of microRNAs and their computationally predicted targets in the rat kidney provides a unique molecular basis for further exploring the biological role of microRNA. In addition, this study establishes a differential profile of microRNA expression between the renal cortex and the renal medulla and greatly expands the known differential proteome profiles between the two kidney regions.


Nucleic Acids Research | 2010

MicroRNA-target pairs in human renal epithelial cells treated with transforming growth factor β1: a novel role of miR-382

Alison J. Kriegel; Yi Fang; Yong Liu; Zhongmin Tian; Domagoj Mladinov; Isaac R. Matus; Xiaoqiang Ding; Andrew S. Greene; Mingyu Liang

We reported previously an approach for identifying microRNA (miRNA)-target pairs by combining miRNA and proteomic analyses. The approach was applied in the present study to examine human renal epithelial cells treated with transforming growth factor β1 (TGFβ1), a model of epithelial–mesenchymal transition important for the development of renal interstitial fibrosis. Treatment of human renal epithelial cells with TGFβ1 resulted in upregulation of 16 miRNAs and 18 proteins and downregulation of 17 miRNAs and 16 proteins. Of the miRNAs and proteins that exhibited reciprocal changes in expression, 77 pairs met the sequence criteria for miRNA–target interactions. Knockdown of miR-382, which was up-regulated by TGFβ1, attenuated TGFβ1-induced loss of the epithelial marker E-cadherin. miR-382 was confirmed by 3′-untranslated region reporter assay to target five genes that were downregulated at the protein level by TGFβ1, including superoxide dismutase 2 (SOD2). Knockdown of miR-382 attenuated TGFβ1-induced downregulation of SOD2. Overexpression of SOD2 ameliorated TGFβ1-induced loss of the epithelial marker. The study provided experimental evidence in the form of reciprocal expression at the protein level for a large number of predicted miRNA-target pairs and discovered a novel role of miR-382 and SOD2 in the loss of epithelial characteristics induced by TGFβ1.


American Journal of Physiology-renal Physiology | 2009

MicroRNA: a new frontier in kidney and blood pressure research

Mingyu Liang; Yong Liu; Domagoj Mladinov; Allen W. Cowley; Hariprasad Trivedi; Yi Fang; Xialian Xu; Xiaoqiang Ding; Zhongmin Tian

MicroRNA (miRNA) has emerged rapidly as a major new direction in many fields of research including kidney and blood pressure research. A mammalian genome encodes several hundred miRNAs. These miRNAs potentially regulate the expression of thousands of proteins. miRNA expression profiles differ substantially between the kidney and other organs as well as between kidney regions. miRNAs may be functionally important in models of diabetic nephropathy, podocyte development, and polycystic disease. miRNAs may be involved in the regulation of arterial blood pressure, including possible involvement in genetic elements of hypertension. Studies of miRNAs could generate diagnostic biomarkers for kidney disease and new mechanistic insights into the complex regulatory networks underlying kidney disease and hypertension. Further progress in the understanding of miRNA biogenesis and action and technical improvements for target identification and miRNA manipulation will be important for studying miRNAs in renal function and blood pressure regulation.


Hypertension | 2008

Renal Regional Proteomes in Young Dahl Salt-Sensitive Rats

Zhongmin Tian; Andrew S. Greene; Kristie Usa; Isaac R. Matus; Jesse Bauwens; Jennifer L. Pietrusz; Allen W. Cowley; Mingyu Liang

We performed an extensive proteomic analysis of the Dahl model of salt-sensitive hypertension. The consomic SS-13BN rat, genetically similar to the Dahl salt-sensitive rat, while exhibiting a significant amelioration of salt-induced hypertension, was used as a control. Proteomic analysis, using differential in-gel electrophoresis and mass spectrometry techniques, was performed in the renal cortex and the renal medulla of 6-week–old SS and SS-13BN rats before significant differences in blood pressure were developed between the 2 strains of rat. Several dozen proteins were identified as differentially expressed between SS and SS-13BN rats fed the 0.4% NaCl diet or switched to the 4% NaCl diet for 3 days (n=4). The identified proteins were involved in cellular functions or structures including signal transduction, energy metabolism, and the cytoskeleton. The proteomic analysis and subsequent Western blotting indicated that heterogeneous nuclear ribonucleoprotein K in the renal medulla was upregulated by the 4% NaCl diet in SS-13BN rats but downregulated in SS rats. The level of angiotensinogen mRNA in the renal medulla was regulated in an opposite manner. Silencing of heterogeneous nuclear ribonucleoprotein K resulted in an upregulation of angiotensinogen in cultured human kidney cells. In summary, we identified significant differences in kidney regional proteomic profiles between SS and SS-13BN rats and demonstrated a potential role of heterogeneous nuclear ribonucleoprotein K in the regulation of angiotensinogen expression in the renal medulla.


Hypertension | 2009

Novel Role of Fumarate Metabolism in Dahl-Salt Sensitive Hypertension

Zhongmin Tian; Yong Liu; Kristie Usa; Domagoj Mladinov; Yi Fang; Xiaoqiang Ding; Andrew S. Greene; Allen W. Cowley; Mingyu Liang

In a previous proteomic study, we found dramatic differences in fumarase in the kidney between Dahl salt-sensitive rats and salt-insensitive consomic SS-13BN rats. Fumarase catalyzes the conversion between fumarate and l-malate in the tricarboxylic acid cycle. Little is known about the pathophysiological significance of fumarate metabolism in cardiovascular and renal functions, including salt-induced hypertension. The fumarase gene is located on the chromosome substituted in the SS-13BN rat. Sequencing of fumarase cDNA indicated the presence of lysine at amino acid position 481 in Dahl salt-sensitive rats and glutamic acid in Brown Norway and SS-13BN rats. Total fumarase activity was significantly lower in the kidneys of Dahl salt-sensitive rats compared with SS-13BN rats, despite an apparent compensatory increase in fumarase abundance in Dahl salt-sensitive rats. Intravenous infusion of a fumarate precursor in SS-13BN rats resulted in a fumarate excess in the renal medulla comparable to that seen in Dahl salt-sensitive rats. The infusion significantly exacerbated salt-induced hypertension in SS-13BN rats (140±3 vs125±2 mm Hg in vehicle control at day 5 on a 4% NaCl diet; P<0.05). In addition, the fumarate infusion increased renal medullary tissue levels of H2O2. Treatment of cultured human renal epithelial cells with the fumarate precursor also increased cellular levels of H2O2. These data suggest a novel role for fumarate metabolism in salt-induced hypertension and renal medullary oxidative stress.


Journal of Ultrasound in Medicine | 2010

Bioeffects of Low-Intensity Ultrasound In Vitro Apoptosis, Protein Profile Alteration, and Potential Molecular Mechanism

Yi Feng; Zhongmin Tian; Mingxi Wan

Objective. The purpose of this study was to evaluate the potential molecular mechanism of low‐intensity ultrasound‐induced apoptosis by analyzing protein profile alteration in response to ultrasound exposure. Methods. Human hepatocarcinoma SMMC‐7721 cells were used in this study. Cell viability was measured by a trypan blue dye exclusion test. Morphologic changes were examined by light microscopy. Apoptosis was assessed by phosphatidylserine externalization and DNA fragmentation. The pattern of the mitochondrial membrane potential decrease was determined by flow cytometry. Protein profile alteration was analyzed by comparative proteomics based on 2‐dimensional polyacrylamide gel electrophoresis and matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry. Results. Low‐intensity ultrasound (3.0 W/cm2, 1 minute, cells incubated for 6 hours after ultrasound exposure) induced early apoptosis (mean ± SD, 26.5% ± 6.2%) significantly (P < .05) with minimal lysis in human hepatocarcinoma cells in vitro. On a molecular level, several proteins, eg, cellular tumor antigen protein 53, BH3‐interacting domain death agonist, apoptosis regulator Bcl‐2, and heme oxygenase 1 were identified as responding to ultrasound irradiation, suggesting that mitochondrial dysfunction and oxidative stresses were involved in ultrasound‐induced apoptosis. It was also assumed that mitofilin‐regulated crista remodeling may be a potential channel of mitochondrial membrane permeabilization pore formation involved in low‐intensity ultrasound‐induced apoptosis. Conclusions. This study suggests that 2 potential molecular signaling pathways are involved in ultrasound‐induced apoptosis. It is a first step toward low‐intensity ultrasound‐induced apoptotic cancer therapy via understanding its relevant molecular signaling and key proteins.


Analytica Chimica Acta | 2015

Reconstruction and analysis of correlation networks based on GC–MS metabolomics data for young hypertensive men

Le Wang; Entai Hou; Lijun Wang; Yanjun Wang; Lingjian Yang; Xiaohui Zheng; Guangqi Xie; Qiong Sun; Mingyu Liang; Zhongmin Tian

The awareness, treatment, and control rates of hypertension for young adults are much lower than average. It is urgently needed to explore the variances of metabolic profiles for early diagnosis and treatment of hypertension. In current study, we applied a GC-MS based metabolomics platform coupled with a network approach to analyze plasma samples from young hypertensive men and age-matched healthy controls. Our findings confirmed distinct metabolic footprints of young hypertensive men. The significantly altered metabolites between two groups were enriched for the biological module of amino acids biosynthesis. The correlations of GC-MS metabolomics data were then visualized as networks based on Pearson correlation coefficient (threshold=0.6). The plasma metabolites identified by GC-MS and the significantly altered metabolites (P<0.05) between patients and controls were respectively included as nodes of a network. Statistical and topological characteristics of the networks were studied in detail. A few amino acids, glycine, lysine, and cystine, were screened as hub metabolites with higher values of degree (k), and also obtained highest scores of three centrality indices. The short average path lengths and high clustering coefficients of the networks revealed a small-world property, indicating that variances of these amino acids have a major impact on the metabolic change in young hypertensive men. These results suggested that disorders of amino acid metabolism might play an important role in predisposing young men to developing hypertension. The combination of metabolomics and network methods would provide another perspective on expounding the molecular mechanism underlying complex diseases.


American Journal of Physiology-renal Physiology | 2014

Ultrastructure of mitochondria and the endoplasmic reticulum in renal tubules of Dahl salt-sensitive rats

Xiaofeng He; Yong Liu; Kristie Usa; Zhongmin Tian; Allen W. Cowley; Mingyu Liang

Metabolic and functional abnormalities in the kidney precede or coincide with the initiation of overt hypertension in the Dahl salt-sensitive (SS) rat. However, renal histological injury in SS rats is mild before the development of overt hypertension. We performed electron microscopy analysis in 7-wk-old SS rats and salt-insensitive consomic SS.13(BN) rats and Sprague-Dawley (SD) rats fed a 4% NaCl diet for 7 days. Long mitochondria (>2 μm) accounted for a significantly smaller fraction of mitochondria in medullary thick ascending limbs in SS rats (4% ± 1%) than in SS.13(BN) rats (8% ± 1%, P < 0.05 vs. SS rats) and SD rats (9% ± 1%, P < 0.01 vs. SS rats), consistent with previous findings of mitochondrial functional insufficiency in the medulla of SS rats. Long mitochondria in proximal tubules, however, were more abundant in SS rats than in SS.13(BN) and SD rats. The width of the endoplasmic reticulum, an index of endoplasmic reticulum stress, was significantly greater in medullary thick ascending limbs of SS rats (107 ± 1 nm) than in SS.13(BN) rats (95 ± 2 nm, P < 0.001 vs. SS rats) and SD rats (74 ± 3 nm, P < 0.01 vs. SS or SS.13(BN) rats). The tubules examined were indistinguishable between rat strains under light microscopy. These data indicate that ultrastructural abnormalities occur in the medullary thick ascending limbs of SS rats before the development of histological injury in renal tubules, providing a potential structural basis contributing to the subsequent development of overt hypertension.


Biochemical and Biophysical Research Communications | 2014

Analysis of metabolites in plasma reveals distinct metabolic features between Dahl salt-sensitive rats and consomic SS.13BN rats

Le Wang; Entai Hou; Zhengjun Wang; Na Sun; Liqing He; Lan Chen; Mingyu Liang; Zhongmin Tian

Salt-sensitive hypertension is a major risk factor for cardiovascular disorders. Our previous proteomic study revealed substantial differences in several proteins between Dahl salt-sensitive (SS) rats and salt-insensitive consomic SS.13(BN) rats. Subsequent experiments indicated a role of fumarase insufficiency in the development of hypertension in SS rats. In the present study, a global metabolic profiling study was performed using gas chromatography/mass spectrometry (GC/MS) in plasma of SS rats (n=9) and SS.13(BN) rats (n=8) on 0.4% NaCl diet, designed to gain further insights into the relationship between alterations in cellular intermediary metabolism and predisposition to hypertension. Principal component analysis of the data sets revealed a clear clustering and separation of metabolic profiles between SS rats and SS.13(BN) rats. 23 differential metabolites were identified (P<0.05). Higher levels of five TCA cycle metabolites, fumarate, cis-aconitate, isocitrate, citrate and succinate, were observed in SS rats. Pyruvate, which connects TCA cycle and glycolysis, was also increased in SS rats. Moreover, lower activity levels of fumarase, aconitase, α-ketoglutarate dehydrogenase and succinyl-CoA synthetase were detected in the heart, liver or skeletal muscles of SS rats. The distinct metabolic features in SS and SS.13(BN) rats indicate abnormalities of TCA cycle in SS rats, which may play a role in predisposing SS rats to developing salt-sensitive hypertension.


Journal of Materials Chemistry B | 2017

Hybrid nanoparticles coated with hyaluronic acid lipoid for targeted co-delivery of paclitaxel and curcumin to synergistically eliminate breast cancer stem cells

Zhe Yang; Na Sun; Rui Cheng; Chenyang Zhao; Jie Liu; Zhongmin Tian

Conventional chemotherapy drugs such as paclitaxel (PTX) can effectively inhibit tumor growth by killing the majority of the proliferating cancer cells; however, it also results in multi-drug resistance (MDR) and facilitates the conversion of non-cancer stem cells (non-CSCs) to cancer stem cells (CSCs), which are considered the reason for chemotherapy resistance, relapse, and metastasis. Thus, exploring combination therapy with multiple chemotherapeutics is considered as a promising approach for simultaneously eliminating CSCs and non-CSCs. Here, we fabricated a bCSC (breast cancer stem cell)-targeting co-delivery system (HA-hybrid NPs) by attaching a lipoid (HA-HDA) to the surface of hydrophobic PLGA nanoparticles to co-deliver the widely used chemotherapy agent, PTX, and the selective inhibitor of CSCs, curcumin (CUR). This co-delivery system was capable of targeting bCSCs via an interaction between HA and the CD44 receptor on the membrane of bCSCs, and it could efficiently eliminate the bCSC population, decrease the mammosphere formation of bCSCs, and inhibit the migration of bCSCs. Most importantly, HA-hybrid co-delivered NPs exhibited enhanced anti-tumor efficacy by synergistically inhibiting the growth of both non-bCSCs and bCSCs on MCF7 xenografted tumor models. Taken together, the results of this study demonstrate that this bCSC-targeted HA-hybrid NP provides a potential strategy for enhancing breast cancer therapeutic efficiency.

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Mingyu Liang

Medical College of Wisconsin

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Entai Hou

Xi'an Jiaotong University

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Na Sun

Xi'an Jiaotong University

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Chenyang Zhao

Xi'an Jiaotong University

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Mingxi Wan

Xi'an Jiaotong University

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Zhe Yang

Sun Yat-sen University

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Kristie Usa

Medical College of Wisconsin

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Yong Liu

Medical College of Wisconsin

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Zerong Liu

Xi'an Jiaotong University

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Rui Cheng

Xi'an Jiaotong University

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