Jian Da Dong

Publications (3)35.1 Total impact

• Article: Activation of the epithelial Na+ channel triggers prostaglandin E₂ release and production required for embryo implantation.

  Ye Chun Ruan, Jing Hui Guo, Xinmei Liu, Runju Zhang, Lai Ling Tsang, Jian Da Dong, Hui Chen, Mei Kuen Yu, Xiaohua Jiang, Xiao Hu Zhang, Kin Lam Fok, Yiu Wa Chung, Hefeng Huang, Wen Liang Zhou, Hsiao Chang Chan
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  ABSTRACT: Embryo implantation remains a poorly understood process. We demonstrate here that activation of the epithelial Na⁺ channel (ENaC) in mouse endometrial epithelial cells by an embryo-released serine protease, trypsin, triggers Ca²⁺ influx that leads to prostaglandin E₂ (PGE₂) release, phosphorylation of the transcription factor CREB and upregulation of cyclooxygenase 2, the enzyme required for prostaglandin production and implantation. We detected maximum ENaC activation, as indicated by ENaC cleavage, at the time of implantation in mice. Blocking or knocking down uterine ENaC in mice resulted in implantation failure. Furthermore, we found that uterine ENaC expression before in vitro fertilization (IVF) treatment is markedly lower in women with implantation failure as compared to those with successful pregnancy. These results indicate a previously undefined role of ENaC in regulating the PGE₂ production and release required for embryo implantation, defects that may be a cause of miscarriage and low success rates in IVF.
  Nature medicine 06/2012; 18(7):1112-7. · 27.14 Impact Factor
• Article: Lymphocyte CFTR promotes epithelial bicarbonate secretion for bacterial killing.

  Xiao Xiao Tang, Kin Lam Fok, Hao Chen, Kay Sheung Chan, Lai Ling Tsang, Dewi Kenneth Rowlands, Xiao Hu Zhang, Jian Da Dong, Ye Chun Ruan, Xiaohua Jiang, Sidney Siu Bun Yu, Yiu Wa Chung, Hsiao Chang Chan
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  ABSTRACT: The expression of cystic fibrosis transmembrane conductance regulator (CFTR) in lymphocytes has been reported for nearly two decades; however, its physiological role remains elusive. Here, we report that co-culture of lymphocytes with lung epithelial cell line, Calu-3, promotes epithelial HCO(3)- production/secretion with up-regulated expression of carbonic anhydrase 2 and 4 (CA-2, CA-4) and enhanced bacterial killing capability. The lymphocyte-enhanced epithelial HCO(3)- secretion and bacterial killing activity was abolished when Calu3 cells were co-cultured with lymphocytes from CFTR knockout mice, or significantly reduced by interfering with E-cadherin, a putative binding partner of CFTR. Bacterial lipopolysaccharide (LPS)-induced E-cadherin and CA-4 expression in the challenged lung was also found to be impaired in CFTR knockout mice compared to that of the wild-type. These results suggest that the interaction between lymphocytes and epithelial cells may induce a previously unsuspected innate host defense mechanism against bacterial infection by stimulating epithelial HCO(3)- production/secretion, which requires CFTR expression in lymphocytes.
  Journal of Cellular Physiology 05/2012; 227(12):3887-94. · 3.87 Impact Factor
• Source

  Available from: Ann Lau

  Article: Defective CFTR-dependent CREB activation results in impaired spermatogenesis and azoospermia.

  Wen Ming Xu, Jing Chen, Hui Chen, Rui Ying Diao, Kin Lam Fok, Jian Da Dong, Ting Ting Sun, Wen Ying Chen, Mei Kuen Yu, Xiao Hu Zhang, Lai Ling Tsang, Ann Lau, Qi Xian Shi, Qing Hua Shi, Ping Bo Huang, Hsiao Chang Chan
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  ABSTRACT: Cystic fibrosis (CF) is the most common life-limiting recessive genetic disease among Caucasians caused by mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) with over 95% male patients infertile. However, whether CFTR mutations could affect spermatogenesis and result in azoospermia remains an open question. Here we report compromised spermatogenesis, with significantly reduced testicular weight and sperm count, and decreased cAMP-responsive element binding protein (CREB) expression in the testes of CFTR knockout mice. The involvement of CFTR in HCO(3) (-) transport and the expression of the HCO(3) (-) sensor, soluble adenylyl cyclase (sAC), are demonstrated for the first time in the primary culture of rat Sertoli cells. Inhibition of CFTR or depletion of HCO(3) (-) could reduce FSH-stimulated, sAC-dependent cAMP production and phosphorylation of CREB, the key transcription factor in spermatogenesis. Decreased CFTR and CREB expression are also observed in human testes with azoospermia. The present study reveals a previously undefined role of CFTR and sAC in regulating the cAMP-CREB signaling pathway in Sertoli cells, defect of which may result in impaired spermatogenesis and azoospermia. Altered CFTR-sAC-cAMP-CREB functional loop may also underline the pathogenesis of various CF-related diseases.
  PLoS ONE 01/2011; 6(5):e19120. · 4.09 Impact Factor