Are you Jiali Dong?

Claim your profile

Publications (5)36.36 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Phosphate homeostasis is critical for many physiological functions. Up to 85% of phosphate is stored in bone and teeth. The remaining 15% is distributed in cells. Phosphate absorption across the brush-border membrane (BBM) of enterocytes occurs mainly via a sodium-dependent pathway, which is mediated by type IIb sodium-phosphate cotransporters (NaPi-IIb). Patients of inflammatory bowel diseases (IBDs) suffer not only from diarrhea and nutrient malabsorption but also from bone loss. About 31-59% of patients with IBD develop bone disorders. Since the intestine is a primary location for dietary phosphate absorption, it is logical to postulate that there is an inverse relationship between gastrointestinal disorders and phosphate transport, which, in turn, contributes to bone disorders observed in patients with IBD. Phosphate absorption and NaPi-IIb expression was studied with BBM vesicles isolated from trinitrobenzene sulphonic acid (TNBS) animals as well as in Caco-2 cells. The mechanism of TNF-alpha downregulation of NaPi-IIb expression was investigated by luciferase assay, gel mobility shift assay (GMSA), and coimmunoprecipitation. Intestinal phosphate absorption mediated by NaPi-IIb was reduced both in TNBS colitis and in TNF-alpha-treated cells. Transient transfection indicated that TNF-alpha inhibits NaPi-IIb expression by reducing NaPi-IIb basal promoter activity. GMSAs identified NF1 protein as an important factor in TNF-alpha-mediated NaPi-IIb downregulation. Signaling transduction study and coimmunoprecipitation suggested that TNF-alpha interacts with EGF receptor to activate ERK1/2 pathway. Intestinal phosphate absorption mediated by NaPi-IIb protein is reduced in colitis. This inhibition is mediated by the proinflammatory cytokine TNF-alpha through a novel molecular mechanism involving TNF-alpha/EGF receptor interaction.
    AJP Gastrointestinal and Liver Physiology 03/2009; 296(4):G775-81. · 3.65 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: NHE8 is a newly identified NHE isoform expressed in rat intestine. To date, the kinetic characteristics and the intestinal segmental distribution of this NHE isoform have not been studied. This current work was performed to determine the gene expression pattern of the NHE8 transporter along the gastrointestinal tract, as well as its affinity for Na(+), H(+), and sensitivity to known NHE inhibitors HOE694 and S3226. NHE8 was differentially expressed along the GI tract. Higher NHE8 expression was seen in stomach, duodenum, and ascending colon in human, while higher NHE8 expression was seen in jejunum, ileum and colon in adult mouse. Moreover, the expression level of NHE8 is much higher in the stomach and jejunum in young mice compared with adult mice. To evaluate the functional characterictics of NHE8, the pH indicator SNARF-4 was used to monitor the rate of intra-cellular pH (pH(i)) recovery after an NH(4)Cl induced acid load in NHE8 cDNA transfected PS120 cells. The NHE8 cDNA transfected cells exhibited a sodium-dependent proton exchanger activity having a Km for pH(i) of approximately pH 6.5, and a Km for sodium of approximately 23 mM. Low concentration of HOE694 (1 microM) had no effect on NHE8 activity, while high concentration (10 microM) significantly reduced NHE8 activity. In the presence of 80 microM S3226, the NHE8 activity was also inhibited significantly. In conclusion, our work suggests that NHE8 is expressed along the gastrointestinal tract and NHE8 is a functional Na(+)/H(+) exchanger with kinetic characteristics that differ from other apically expressed NHE isoforms.
    Cellular Physiology and Biochemistry 02/2008; 21(1-3):109-16. · 3.42 Impact Factor
  • Gastroenterology 01/2008; 134(4). · 12.82 Impact Factor
  • Gastroenterology 01/2008; 134(4). · 12.82 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Our previous studies have identified a minimal Sp1-driven promoter region (nt -36/+116) directing NHE2 expression in mouse renal epithelial cells. However, this minimal promoter region was not sufficient to support active transcription of NHE2 gene in the intestinal epithelial cells, suggesting the need for additional upstream regulatory elements. In the present study, we used nontransformed rat intestinal epithelial (RIE) cells as a model to identify the minimal promoter region and transcription factors necessary for the basal transcription of rat NHE2 gene in the intestinal epithelial cells. We identified a region within the rat NHE2 gene promoter located within nt -67/-43 upstream of transcription initiation site as indispensable for the promoter function in intestinal epithelial cells. Mutations at nt -56/-51 not only abolished the DNA-protein interaction in this region, but also completely abolished NHE2 gene promoter activity in RIE cells. Supershift assays revealed that Sp1 and Sp3 interact with this promoter region, but, contrary to the minimal promoter indispensable for renal expression of NHE2, both transcription factors expressed individually in Drosophila SL2 cells activated rat NHE2 gene promoter. Moreover, Sp1 was a weaker transactivator and when coexpressed in SL2 cells it reduced Sp3-mediated NHE2 basal promoter activity. Furthermore, DNase I footprinting confirmed that nt -58/-51 is protected by nuclear protein from RIE cells. We conclude that the mechanism of basal control of rat NHE2 gene promoter activity is different in the renal and intestinal epithelium, with Sp3 being the major transcriptional activator of NHE2 gene transcription in the intestinal epithelial cells.
    AJP Gastrointestinal and Liver Physiology 08/2007; 293(1):G146-53. · 3.65 Impact Factor