Zhihong Yang

Publications (10)29.07 Total impact

• Article: Serum Angptl2 levels are independently associated with albuminuria in type 2 diabetes.

  Qin Li, Wei Gong, Zhihong Yang, Bin Lu, Yehong Yang, Weiwei Zhao, Renming Hu
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  ABSTRACT: BACKGROUND: Elevated serum Angptl2 levels are positively associated with the development of type 2 diabetes. We investigated whether serum Angptl2 levels are associated with diabetic nephropathy in patients with type 2 diabetes. METHODS: Two hundred and thirty patients with type 2 diabetes and 63 healthy controls participated in this cross-sectional study. Subjects with type 2 diabetes were divided into three groups using urinary albumin-to-creatinine ratio (ACR): a normoalbuminuric group (n=57), a microalbuminuric group (n=130) and a macroalbuminuria group (n=43). Serum Angptl2 concentrations were measured by enzyme-linked immunosorbent assay. RESULTS: Median serum (interquartile range) Angptl2 levels in control subjects and patients with type 2 diabetes with normoalbuminuria, microalbuminuria and macroalbuminuria were 24.03 (16.3-33.45), 36.14 (27.91-43.07), 44.6 (37.47-49.92), 50.19 (45.95-60.13)ng/ml (p<0.01) respectively. Angptl2 levels correlated with urinary ACR in participants with type 2 diabetes (r=0.38, p<0.01). Significant intercorrelations of Angptl2 were found with age, duration of diabetes, and fasting plasma glucose. After adjustment for significant covariates, albuminuria was still significantly associated with Angptl2 levels in type 2 diabetes (r=0.31, p<0.01). CONCLUSIONS: Angptl2 levels are elevated in patients with type 2 diabetes with an independent association between increasing Angptl2 levels and increasing levels of albuminuria. This suggests a possible role of Angptl2 in progressive nephropathy in patients with type 2 diabetes.
  Diabetes research and clinical practice 04/2013; · 2.16 Impact Factor
• Article: Aspirin reduces the apoptotic effect of etoposide via Akt activation and up-regulation of p21(cip).

  Xiaocheng Feng, Bin Lu, Yingying Xu, Qin Li, Wenbai Zhou, Zhihong Yang, Zeng Yang, Weiwei Zhao, Zonghou Shen, Renming Hu
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  ABSTRACT: Previous studies on the apoptotic effect of aspirin mainly focus on colorectal cancer and breast carcinoma. Few studies have been designed to explore the effect of aspirin on hepatocellular carcinoma. In the present study, we observed that aspirin caused G0/G1 phase cell cycle arrest and reduced etoposide induced caspase-3 activation in hepatocellular carcinoma G2 (HepG2) cells. Further investigation demonstrated that aspirin notably enhanced the activity of Akt and ERK1/2. Blocking the activation of Akt by the PI3-K-selective inhibitor wortmannin abrogated the anti-apoptotic effect of aspirin while the MEK inhibitor U0126 did not. p21(cip), an important substrate of Akt, is involved in the regulation of cell cycle arrest and apoptosis. Our data showed that the protein expression and ser146 phosphorylation levels of p21(cip) were significantly increased after treatment with aspirin, whereas p53 or p27 showed no change. The increase of p21(cip) protein levels was also scavenged by wortmannin but not by U0126. Moreover, reduction of caspase-3 activity induced by aspirin was attenuated by silencing p21(cip) expression. These results indicated that the anti-apoptotic effect of aspirin was dependent on activation of Akt which inhibited cell apoptosis by up-regulating p21(cip) and blocking caspase-3 activation. These findings could have clinical relevance in anticancer therapy and aspirin co-treatment of human malignancies.
  International Journal of Molecular Medicine 05/2011; 28(4):637-43. · 1.98 Impact Factor
• Article: Identification of the novel protein FAM172A, and its up-regulation by high glucose in human aortic smooth muscle cells.

  Lianxi Li, Xuehong Dong, Man Cheong Leong, Wenbai Zhou, Zhihong Yang, Fengling Chen, Yuqian Bao, Weiping Jia, Renming Hu
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  ABSTRACT: The family with sequence similarity 172, member A (FAM172A) is a hypothetical protein. We recently cloned the FAM172A gene from normal human aortic tissues. In a previous study we also showed that the FAM172A gene was up-regulated by high glucose levels in macrophages. In the present study, we further identified the FAM172A protein at the level of translation and studied the effects of high glucose levels on its expression in human aortic smooth muscle cells. The FAM172A gene was subcloned into the eukaryotic expression vectors, PDC315 and pEGFP-N2. The cloned sequence shows an open reading frame of 1251 nucleotides encoding a protein of 416 amino acids. We further expressed the recombinant FAM172A protein and generated rabbit anti-human FAM172A polyclonal antibodies. The FAM172A protein was identified for the first time at the translation level by Western blot analysis. Western blotting also demonstrated that the FAM172A protein could be detected in human aortic endothelial, human aortic smooth muscle cells and THP-1-derived macrophages, the highest expression being observed in the human aortic smooth muscle cells. By a combination of bioinformatics and confocal laser scanning microscopy, we found that the FAM172A protein in HEK293 cells, was mainly located in the nucleus, and that there was an Arb2 conserved domain in the FAM172A protein sequence. We also presented evidence that the FAM172 protein expression in human aortic smooth muscle cells was up-regulated by high glucose levels in a concentration-dependent and time-course manner. We speculated that as a novel protein, FAM172A could be involved in the pathogenesis of high glucose-induced vascular damage.
  International Journal of Molecular Medicine 10/2010; 26(4):483-90. · 1.98 Impact Factor
• Article: Elevated serum chemokine CXC ligand 5 levels are associated with hypercholesterolemia but not a worsening of insulin resistance in Chinese people.

  Zhen Yang, Zhaoyun Zhang, Jie Wen, Xuanchun Wang, Bin Lu, Zhihong Yang, Weiwei Zhang, Mei Wang, Xiaocheng Feng, Charlotte Ling, Songhua Wu, Renming Hu
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  ABSTRACT: Recent study showed high chemokine CXC ligand 5 (CXCL5) is thought to be associated with insulin resistance in humans. However, evidence from large-scale populations about the relationship between serum CXCL5 level and metabolic phenotypes is scarce. Here we sought to evaluate serum CXCL5 distribution and its association with metabolic phenotypes among middle-aged and older Chinese. We evaluated serum CXCL5 in a cross-sectional sample of 3225 Chinese aged from 50 to 88 yr in a Shanghai downtown district by ELISA. Glucose, insulin, lipid profile, inflammatory marker, and adipokine were also measured. The crude mean of serum CXCL5 concentrations were 1493.31 pg/ml for men and 2059.42 pg/ml for women (P<0.001), respectively. After multiple adjustment, the odds ratios were substantially higher for hypercholesterolemia (odds ratio 3.26, 95% confidence interval 2.36-4.51) in the highest CXCL5 quartile compared with those in the lowest quartile. These associations remained significant after further adjustment for body mass index, body fat, inflammatory marker, and adipokine. However, serum resistin CXCL5 was not associated with body mass index, percent body fat, fasting glucose, insulin levels, and homeostasis model assessment index-insulin resistance (r=0.01, 0.01, 0.01, 0.04, and 0.03, respectively; all P>0.05). Elevated circulating CXCL5 concentrations were associated with higher risk of hypercholesterolemia in middle-aged and elderly Chinese independent of obesity, inflammation, adipokines, and other risk factors but not insulin resistance.
  The Journal of clinical endocrinology and metabolism 08/2010; 95(8):3926-32. · 6.50 Impact Factor
• Article: High prevalence of diabetic neuropathy in population-based patients diagnosed with type 2 diabetes in the Shanghai downtown.

  Bin Lu, Zhihong Yang, Mei Wang, Zhen Yang, Wei Gong, Yehong Yang, Jie Wen, Zhaoyun Zhang, Naiqing Zhao, Xixing Zhu, Renming Hu
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  ABSTRACT: To determine the prevalence of diabetic peripheral neuropathy (DPN) and risk factors associated with DPN in type 2 diabetic patients. 435 diabetic patients were evaluated on complete foot examination. Body mass measurements, resting blood pressure, fasting blood measures, urinary albumin-to-creatinine ratio (ACR) and the digitally stored fundus images were investigated. (1) The prevalence of DPN was 61.8% among the Chinese patients diagnosed with type 2 diabetes aged over 30 in the Shanghai downtown, 59.1% with vibration perception threshold > or =25 V and 13.8% with inability to feel the monofilament. (2) DPN was significantly associated with age (beta: 0.068, S.E.: 0.013, OR: 1.070, CI: 1.043-1.098, P<0.001) and HbA1c (beta: 0.224, S.E.: 0.081, OR: 1.251, CI: 1.067-1.466, P=0.006) by a logistic regression analysis. (3) The percentage of diabetic retinopathy (DR) in the DPN group (26.5%) was significantly higher than that in the non-DPN group (15.2%). (4) The percentage of macroalbuminuria in the DPN group (9.0%) was significantly higher than that in the non-DPN group (1.8%). The prevalence of DPN observed in the Chinese patients diagnosed with type 2 diabetes aged over 30 in the Shanghai downtown reached up to 61.8% though the observations in our study might be representative of the diabetic patients of the Shanghai downtown.
  Diabetes research and clinical practice 03/2010; 88(3):289-94. · 2.16 Impact Factor
• Article: Molecular cloning of a novel nuclear factor, TDRP1, in spermatogenic cells of testis and its relationship with spermatogenesis.

  Xuanchun Wang, Haowen Jiang, Wenbai Zhou, Zhaoyun Zhang, Zhihong Yang, Yong Lu, Bin Lu, Xiang Wang, Qiang Ding, Renming Hu
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  ABSTRACT: We reported the identification of a novel gene termed TDRP (encoding testis development-related protein) that might be involved in spermatogenesis. The human TDRP gene had two distinct transcripts, TDRP1 and TDRP2, which encoded proteins of 183 aa and 198 aa respectively. Tdrp mRNA was predominantly expressed in testis tissue. We generated rabbit polyclonal antibodies specific against human TDRP1. Immunohistochemistry analysis showed TDRP1 was expressed in spermatogenic cells, especially with high expression in spermatocytes. We provided evidence that TDRP1 distributed in both cytoplasm and nuclei of spermatogenic cells. Expression patterns of Tdrp1 mRNA and its protein were investigated in the rat testis tissues of different developmental stages. Both Tdrp1 mRNA and its protein were barely detected in the testis of neonatal rats, increased remarkably at 3weeks postpartum, and peaked at 2months postpartum. We also investigated TDRP1 expressions in testis tissues of azoospermic men with defective spermatogenesis. Western blot analysis showed that TDRP1 expressions were significantly lower in the testis tissues of azoospermic men compared with normal controls. These current data demonstrated that as a nuclear factor, TDRP1 might play an important role in spermatogenesis.
  Biochemical and Biophysical Research Communications 02/2010; 394(1):29-35. · 2.48 Impact Factor
• Source

  Available from: PubMed Central

  Article: Insulin resistance in Chinese patients with type 2 diabetes is associated with C-reactive protein independent of abdominal obesity.

  Bin Lu, Yehong Yang, Zhihong Yang, Xiaocheng Feng, Xuanchun Wang, Zhaoyun Zhang, Renming Hu
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  ABSTRACT: There is debate as to whether the association between C-reactive protein (CRP) and insulin resistance is independent of body fatness, particularly central obesity. Therefore, the association among CRP, insulin resistance and obesity was analyzed in Chinese patients with type 2 diabetes. The study included 520 Chinese patients diagnosed with type 2 diabetes with CRP levels not exceeding 10 mg/L. The degree of insulin resistance was determined with the homeostasis model assessment of insulin resistance (HOMA-IR). The CRP levels were categorized into quartiles from the lowest to the highest concentrations (Q1-Q4). Body mass index (BMI) and waist circumference (WC) were both higher in Q4, Q3 and Q2 than those in Q1. HOMA-IR was higher in Q2, Q3 and Q4 than that in Q1 (Q1 vs Q4, P < 0.001; Q1 vs Q3, P < 0.001; Q1 vs Q2, P = 0.028). Log CRP was significantly correlated with log HOMA-IR (correlation coefficient: 0.230, P < 0.001) and BMI (correlation coefficient: 0.305, P < 0.001) and WC (correlation coefficient: 0.240, P < 0.001) by Spearman correlation analysis. Multiple linear regression analysis adjusting for age, gender and components of metabolic syndrome, log CRP was also independently associated with log HOMA-IR (β coefficient, 0.168; P < 0.001) and WC (β coefficient, 0.131; P = 0.006). These findings showed that insulin resistance was associated with CRP levels independent of abdominal obesity in Chinese patients with type 2 diabetes, suggesting that abdominal obesity could only partly explain the link between subclinical inflammation and insulin resistance.
  Cardiovascular Diabetology 01/2010; 9:92. · 3.35 Impact Factor
• Article: Depletion of tubulin polymerization promoting protein family member 3 suppresses HeLa cell proliferation.

  Wenbai Zhou, Xuanchun Wang, Lianxi Li, Xiaocheng Feng, Zhihong Yang, Weiwei Zhang, Renming Hu
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  ABSTRACT: Microtubules (MTs) play an important role in cell division, and their functions are regulated by a set of microtubule-associated proteins (MAPs). Tubulin polymerization promoting protein family member 3 (TPPP3), also known as p20, is a new member of the tubulin polymerization promoting protein (TPPP) family. Previous studies have demonstrated that TPPP3 specifically binds to MTs and positively regulates MTs assembly, which leads to significant ultrastructural alterations of the MTs network. However, the physiological function of TPPP3 is still largely unknown. In the present study, we showed that knockdown of endogenous TPPP3 by RNA interference (RNAi) suppressed cell proliferation and induced cell cycle arrest in HeLa cells. Furthermore, we showed that the depletion of TPPP3 caused mitotic abnormalities, such as the formation of multipolar spindles and chromosome segregation errors, which lead to apoptosis in HeLa cells. Our study suggested that TPPP3 played a crucial role in cell mitosis by regulating centrosomes amplification and/or spindles translocation processes.
  Molecular and Cellular Biochemistry 08/2009; 333(1-2):91-8. · 2.06 Impact Factor
• Article: Molecular cloning of a novel secreted peptide, INM02, and regulation of its expression by glucose.

  Xuanchun Wang, Wei Gong, Yu Liu, Zhihong Yang, Wenbai Zhou, Mei Wang, Zhen Yang, Jie Wen, Renming Hu
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  ABSTRACT: We report the identification of a novel secreted peptide, INM02. The mRNA transcript of human INM02 gene is about 3.0 kb. Its open-reading frame contains 762 bps and encodes a protein of 254 amino acids. Northern blot analysis demonstrates that INM02 mRNA is widely expressed in rat tissues, especially with abundant quantities in pancreatic islets, testis, and bladder tissue. We have expressed recombinant INM02 protein and generated rabbit anti-INM02 polyclonal antibodies. We show here that INM02 could be detectable in human serum by ELISA. We also present evidence that INM02 mRNA expression could be regulated by glucose. Experiments on both MIN6 cells and intact isolated islets demonstrate that INM02 mRNA levels are increased more than threefold by high glucose (25 mM) when compared with low glucose (5.5 mM). ELISA analysis shows that secretion of INM02 is significantly augmented by high glucose in vitro. It is speculated that as a novel secreted protein, INM02 is associated with functions of pancreatic islets, especially of beta-cells.
  Journal of Endocrinology 08/2009; 202(3):355-64. · 3.55 Impact Factor
• Article: Increased beta-cell apoptosis and impaired insulin signaling pathway contributes to the onset of diabetes in OLETF rats.

  Jiawei Zhao, Nina Zhang, Min He, Zhihong Yang, Wei Tong, Qinghua Wang, Renming Hu
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  ABSTRACT: Inappropriate adaptation of beta-cell mass is a primary cause of the development of diabetic hyperglycemia. However, the mechanisms underlying regulation of the beta-cell mass in response to insulin resistance or in the development of type 2 diabetes remain unclear. We determined the insulin signaling in the beta-cells and the adaptation of the beta-cell mass in response to the progression of insulin resistance in OLETF rats. By 25 weeks of age, at the onset of diabetes, compared to control LETO rats, OLETF rats developed obesity (Body weight: LETO vs OLETF = 474.0+/-9.5 vs 581.3+/-21.8 g, P < 0.001, n=6), hyperlipidemia (Cholesterol: LETO vs OLETF = 1.67+/-0.07 vs 2.19+/-0.20 mM, P < 0.05, n=6; triglyceride: LETO vs OLETF = 0.36+/-0.05 vs 1.36+/-0.12 mM, P < 0.001, n=6), and impaired glucose tolerance (AUC: LETO vs OLETF = 10.3+/-3.4 vs 29.6+/-7.8 mM, P < 0.001, n=6). Insulin sensitivities as assessed by the insulin sensitivity index (ISI) and the homeostasis model assessment (HOMA) indicated that OLETF rats developed severe insulin resistance. The measurement of plasma insulin levels by ELISA demonstrated, at the onset of diabetes, that fasting insulin levels were increased by 1.2-fold, and 2 hr postprandial insulin levels were increased by 3-fold (P < 0.05, n=6) in OLETF rats compared to age-matched LETO mates which is suggestive of hyperinsulinemia. Immunostaining detected a significant reduction in the insulin receptor substrate 1 (IRS1) (by 54%, P < 0.001) and IRS2 (by 55%, P < 0.001) in the beta-cells of the OLETF rats. Interestingly, while the beta-cell mass was found to be increased (by 2.2-fold; P < 0.001), the beta-cell insulin content as determined by immunostaining was significantly reduced by 32% (P < 0.001) in the OLETF rats when compared to the controls. Our findings suggest that despite increasing beta-cell mass the impaired beta-cell insulin signaling and reduced beta-cell insulin content may contribute to the onset of overt diabetes in OLETF rats.
  Cellular Physiology and Biochemistry 01/2008; 21(5-6):445-54. · 2.86 Impact Factor