About the Authors

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

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

Velidi H Rao

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

Dominic Cosgrove

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

Jean-Philippe Rougier

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

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

Charles F Shield III

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

Zena Werb

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

Raghu Kalluri

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

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.