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Research Article

Stage-Specific Action of Matrix Metalloproteinases Influences Progressive Hereditary Kidney Disease

  • Michael Zeisberg,

    Affiliation: Center for Matrix Biology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, United States of America

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  • Mona Khurana,

    Affiliation: Center for Matrix Biology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, United States of America

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  • Velidi H Rao,

    Affiliation: Gene Expression Laboratory, Boys Town National Research Hospital, Omaha, Nebraska, United States of America

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  • Dominic Cosgrove,

    Affiliation: Gene Expression Laboratory, Boys Town National Research Hospital, Omaha, Nebraska, United States of America

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  • Jean-Philippe Rougier,

    Affiliation: Department of Anatomy, University of California San Francisco, San Francisco, California, United States of America

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  • Michelle C Werner,

    Affiliation: Center for Matrix Biology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, United States of America

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  • Charles F Shield III,

    Affiliation: Department of Surgery, University of Kansas School of Medicine, Wichita, Kansas, United States of America

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  • Zena Werb,

    Affiliation: Department of Anatomy, University of California San Francisco, San Francisco, California, United States of America

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  • Raghu Kalluri mail

    To whom correspondence should be addressed. E-mail: rkalluri@bidmc.harvard.edu

    Affiliations: Center for Matrix Biology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, United States of America, Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts, United States of America, Harvard–MIT Division of Health Sciences and Technology, Boston, Massachusetts, United States of America, Division of Nephrology, Children's Hospital and Harvard Medical School, Boston, Massachusetts, United States of America

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  • Published: March 07, 2006
  • DOI: 10.1371/journal.pmed.0030100

About the Authors

Michael Zeisberg, Mona Khurana, Michelle C Werner, Raghu Kalluri
Center for Matrix Biology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, United States of America
Velidi H Rao, Dominic Cosgrove
Gene Expression Laboratory, Boys Town National Research Hospital, Omaha, Nebraska, United States of America
Jean-Philippe Rougier, Zena Werb
Department of Anatomy, University of California San Francisco, San Francisco, California, United States of America
Charles F Shield III
Department of Surgery, University of Kansas School of Medicine, Wichita, Kansas, United States of America
Raghu Kalluri
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts, United States of America
Raghu Kalluri
Harvard–MIT Division of Health Sciences and Technology, Boston, Massachusetts, United States of America
Raghu Kalluri
Division of Nephrology, Children's Hospital and Harvard Medical School, Boston, Massachusetts, United States of America

Corresponding Author

Email: rkalluri@bidmc.harvard.edu

Competing Interests

The authors have declared that no competing interests exist.

Author Contributions

MZ, ZW, and RK designed the study. MZ and RK analyzed the data. MZ, MK, VHR, DC, JPR, and MCW collected data or carried out experiments for the study. CFS enrolled patients. MZ, VHR, DC, ZW, and RK contributed to writing the paper. DC participated in the electron microscopy studies and in situ zymography. JPR generated and provided the MMP-2 and MMP-9 double-knock-out mice used in this study and designed the conditions for their phenotypic and genotypic characterization. MCW conducted the experiments using Col4A3-deficient mice. ZW helped design the study and assisted with ZW's postdoctorate. J-PR assisted with cross-referencing. CFS provided nephrectomy specimens from patients with Alport syndrome and specimens from pre-renal-failure patients to help confirm portions of the theories.