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Featured researches published by Jianqing Lin.


American Journal of Pathology | 2000

Heparin-Binding EGF-Like Growth Factor Is Up-Regulated in the Obstructed Kidney in a Cell- and Region-Specific Manner and Acts to Inhibit Apoptosis

Hiep T. Nguyen; Samuel H. Bride; Abdel-Basset Badawy; Rosalyn M. Adam; Jianqing Lin; Anna Orsola; Paul D. Guthrie; Michael R. Freeman; Craig A. Peters

The expression of certain growth factors in the epidermal growth factor (EGF) family is altered in response to renal injury. Recent studies have demonstrated that heparin binding EGF-like growth factor (HB-EGF) expression may be cytoprotective in response to apoptotic signals. The purpose of this study was to investigate the potential role of HB-EGF in the upper urinary tract following unilateral ureteral obstruction. We present evidence that: i) ureteral obstruction induced cell-specific but transient activation of HB-EGF gene expression; ii) HB-EGF expression in renal epithelial cells increased under conditions where mechanical deformation, such as that caused by hydronephrotic distension, induces apoptosis, but HB-EGF expression did not increase in renal pelvis smooth muscle cells under identical conditions; and iii) enforced expression of HB-EGF served to protect renal epithelial cells from stretch-induced apoptosis. These results suggest a potential mechanism by which the kidney protects itself from apoptosis triggered by urinary tract obstruction.


Journal of Cellular Biochemistry | 2005

An oxidative stress mechanism mediates chelerythrine‐induced heparin‐binding EGF‐like growth factor ectodomain shedding

Jayoung Kim; Jianqing Lin; Rosalyn M. Adam; Carolyn C. Lamb; Sharon Baughman Shively; Michael R. Freeman

Regulated shedding of cell surface proteins is a mechanism for rapid activation of autocrine and paracrine signaling. Here we report that chelerythrine, a protein kinase C (PKC) inhibitor that possesses a variety of biological functions, is a potent inducer of heparin‐binding epidermal growth factor‐like growth factor (HB‐EGF) shedding from the cell surface. Chelerythrine induced a time‐ and dose‐dependent shedding of an HB‐EGF–alkaline phosphatase (HB‐EGF‐AP) fusion protein expressed in MC2 rat prostate epithelial cells. The soluble form of HB‐EGF‐AP bound to heparin and exhibited potent biological activity as measured by DNA synthesis assay. Chelerythrine‐induced HB‐EGF shedding was metalloproteinase‐(MMP‐) mediated because specific MMP antagonists inhibited shedding by ≥60%. Chelerythrine stimulated production of reactive oxygen species, and antioxidants prevented chelerythrine‐induced HB‐EGF shedding, suggesting that the production of intracellular peroxides is necessary for this event. Consistent with this possibility, antioxidant‐ and MMP‐inhibitable shedding was also demonstrated when hydrogen peroxide was used as an inducer. Although JNK/SAPK and p38 MAPK pathways were activated by chelerythine, these signaling mechanisms were not required to mediate the shedding event. However, JNK signaling was involved in chelerythrine‐stimulated apoptosis. Our results suggest that HB‐EGF shedding induced by chelerythrine is mediated predominantly via the production of reactive oxygen species.


The Journal of Urology | 2001

HEPARIN-BINDING EPIDERMAL GROWTH FACTOR-LIKE GROWTH FACTOR IS AN AUTOCRINE MEDIATOR OF HUMAN PROSTATE STROMAL CELL GROWTH IN VITRO

Jose Luis F. Duque; Rosalyn M. Adam; John S. Mullen; Jianqing Lin; Jerome P. Richie; Michael R. Freeman

PURPOSE The physiological mechanisms by which soluble mediators of cell proliferation and survival alter expansion of the prostatic stroma in benign prostatic hyperplasia are poorly understood. We recently identified heparin-binding epidermal growth factor like growth factor (HB-EGF) as a product predominantly of the smooth muscle cell compartments of the adult human prostate. We assess the potential role of this growth factor as a stromal cell regulator. MATERIALS AND METHODS Primary cultures of desmin and alpha-actin positive human prostate stromal cells were shown to express several cell associated HB-EGF isoforms as well as the primary cognate HB-EGF receptor, ErbB1/HER1, suggesting the existence of an autocrine or juxtacrine regulatory loop. The related receptor tyrosine kinase, ErbB2/HER2, was also expressed as assessed by reverse transcriptase (RT) polymerase chain reaction (PCR). HB-EGF messenger RNA levels in human prostate stromal cells increased modestly (70%) in response to a repetitive mechanical stimulus, a lower response than has been reported for neonatal rat bladder smooth muscle cells, in which HB-EGF was originally identified as a mechanically responsive gene. RESULTS HB-EGF, epidermal growth factor and basic fibroblast growth factor stimulated human prostate stromal cell growth, while a specific antagonist of HB-EGF, [Glu52]-diphtheria toxin/CRM197, inhibited human prostate stromal growth in serum-free medium by a mechanism that did not involve increased apoptosis. A function blocking antibody against CD9/DRAP27/MRP-1, a cell surface binding partner of the membrane form of HB-EGF, also stimulated human prostate stromal cell proliferation. CONCLUSIONS HB-EGF is an endogenously produced human prostate stromal cell growth factor and, thus, may have a role as a physiologically relevant autocrine or juxtacrine mediator of stromal expansion in benign prostatic hyperplasia.


Cancer Research | 2002

Cholesterol-rich Lipid Rafts Mediate Akt-regulated Survival in Prostate Cancer Cells

Liyan Zhuang; Jianqing Lin; Michael L. Lu; Keith R. Solomon; Michael R. Freeman


Cancer Research | 1999

The Phosphatidylinositol 3′-kinase Pathway Is a Dominant Growth Factor-activated Cell Survival Pathway in LNCaP Human Prostate Carcinoma Cells

Jianqing Lin; Rosalyn M. Adam; Eric Santiestevan; Michael R. Freeman


Journal of Biological Chemistry | 2001

BAG-1 Is a Novel Cytoplasmic Binding Partner of the Membrane Form of Heparin-binding EGF-like Growth Factor A UNIQUE ROLE FOR proHB-EGF IN CELL SURVIVAL REGULATION

Jianqing Lin; Lloyd Hutchinson; Sandra M. Gaston; Gerhard Raab; Michael R. Freeman


Endocrinology | 2002

Heparin-Binding Epidermal Growth Factor-Like Growth Factor Stimulates Androgen-Independent Prostate Tumor Growth and Antagonizes Androgen Receptor Function

Rosalyn M. Adam; Jayoung Kim; Jianqing Lin; Anna Orsola; Liyan Zhuang; Dana C. Rice; Michael R. Freeman


Cancer Research | 2003

A Nuclear Form of the Heparin-binding Epidermal Growth Factor-like Growth Factor Precursor Is a Feature of Aggressive Transitional Cell Carcinoma

Rosalyn M. Adam; Theodora E. Danciu; Dawn L. McLellan; Joseph G. Borer; Jianqing Lin; David Zurakowski; Michael Weinstein; Paul H. Rajjayabun; J. Kilian Mellon; Michael R. Freeman


The Prostate | 2003

Transactivation of ErbB1 and ErbB2 receptors by angiotensin II in normal human prostate stromal cells

Jianqing Lin; Michael R. Freeman


The Journal of Urology | 1999

HEPARIN-BINDING EGF-LIKE GROWTH FACTOR IS AN AUTOCRINE AND POSSIBLY JUXTACRINE REGULATOR OF HUMAN PROSTATE SMOOTH MUSCLE CELL GROWTH

Jose Luis F. Duque; John S. Mullen; Jianqing Lin; Rosalyn M. Adam; Joseph G. Borer; Jerome P. Richie; Michael R. Freeman

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Michael R. Freeman

Cedars-Sinai Medical Center

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Rosalyn M. Adam

Boston Children's Hospital

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Jayoung Kim

Cedars-Sinai Medical Center

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Jerome P. Richie

Brigham and Women's Hospital

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John S. Mullen

Brigham and Women's Hospital

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Jose Luis F. Duque

Brigham and Women's Hospital

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Joseph G. Borer

Boston Children's Hospital

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Liyan Zhuang

Boston Children's Hospital

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Paul D. Guthrie

Brigham and Women's Hospital

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