The Molecular and Cellular Biology ofWound Repair Second Edition The Molecular and Cellular Biology of Wo und Repair Second Edition Edited by Richard A. F. Clark State University 0/ New York at Stony Brook Stony Brook. New York SPRINGER SCIENCE+BUSINESS MEDIA, LLC L i b r a r y of Congress Cataloging-in-Publication Data The molecular and c e l l u l a r biology of wound r e p a i r / e d i t e d by Richard A . F . C l a r k . ~ 2nd ed. p. era. Includes b i b l i o g r a p h i c a l references and index. ISBN 978-1-4899-0187-3 1 . Wound h e a l i n g . I . C l a r k , R. A. F. (Richard A . F . ) RD94.M65 1996 617.1—dc20 95-47850 C1P Front cover: Photomicrographs of central granulation tissue in porcine cutaneous wounds at day 5 (left panel), day 7 (middle panel), and day 10 (right panel) that had been formalin-fixed and stained with Masson's trichrome. On day 5 blood vessels are vertically aligned while fibroblasts are randomly oriented in a collagen-poor provisional matrix. By day 7 much collagen (seen as blue fibrils on the original photomicrograph) has been deposited in the granulation tissue. The blood vessels continue to course through the wound vertically while the fibroblasts have assumed a horizontal alignment. At day 10 the granulation tissue has become collagen-rich and blood vessels have diminished in number. Fibroblasts have become stretched across the wound in a strict horizontal orientation as they contract the wound. This book is about the cell-matrix-cytokine interactions that drive this well-regulated progression of events called wound repair. ISBN 978-1-4899-0187-3 ISBN 978-1-4899-0185-9 (eBook) DOI 10.1007/978-1-4899-0185-9 © Springer Science+Business Media New York 1988 Originally published by Plenum Press, New York in 1988 Softcover reprint of the hardcover 2nd edition 1988 10 9 8 7 6 5 4 3 2 A l l rights reserved No part of this book may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, microfilming, recording, or otherwise, without written permission from the Publisher Contributors Judith A. Abraham Scios Nova Inc., Mountain View, Califomia 94043 Monique Aumailley Institute ofProtein Biology and Chemistry, CNRS, 69367 Lyon cedex 7, France Merton Dernfield Joint Program in Neonatology, Harvard Medical School, Boston Children's Hospital, Boston, Massachusetts 02115 Richard A. F. Clark Department of Dermatology, Health Sciences Center, State University of New York at Stony Brook, Stony Brook, New York 11794-8165 Alexis Desmouliere Department of Pathology, University of Geneva, 1211 Geneva 4, Switzerland; and CNRS-URA 1459, Institut Pasteur de Lyon, 69365 Lyon cedex 7, France Deate Eckes Department of Dermatology, University of Cologne, D-50924 Cologne, Germany M. w. J. Ferguson School of Biological Sciences, University of Manchester, Man- chester M 13 9PT, England Leo T. Furcht Department ofLaboratory Medicine and Pathology, Biomedical Engi- neering Center, University of Minnesota, Minneapolis, Minnesota 55455 Giulio Gabbiani Department of Pathology, University of Geneva, 1211 Geneva 4, Switzerland James Gailit Department of Dermatology, Health Sciences Center, School of Medi- eine, State University of New York at Stony Brook, Stony Brook, New York 11794-8165 Richard L. Gallo Department of Dermatology, Harvard Medical School, Boston Children's Hospital, Boston, Massachusetts 02115 v vi Contributors Christopher Haslett Respiratory Medicine Unit, Department of Medicine, Uni ver- sity of Edinburgh, Royal Infirmary, Edinburgh EH3 9YW, Scotland Carl-Henrik Heidin Ludwig Institute for Cancer Research, Biomedical Center, S-751 24 Uppsala, Sweden Peter Henson Departments of Medicine and Pathology, National Jewish Center for Immunology and Respiratory Medicine, Denver, Colorado 80206 Joji Iida Department of Laboratory Medicine and Pathology, Biomedical Engineer- ing Center, University of Minnesota, Minneapolis, Minnesota 55455 L10yd E. King, Jr. Departments of Plastic Surgery, Cell Biology, and Dermatology, Vanderbilt University Medical Center, Department of Veteran's Affairs, Nashville, Tennessee 37232-2631 Michael Klagsbrun Departments of Surgery and Pathology, Children's Hospital, and Harvard Medical School, Boston, Massachusetts 02115 Thomas Krieg Department of Dermatology, University of Cologne, D-50924 Co- logne, Germany Joseph A. Madri Department of Pathology, Yale University School of Medicine, New Haven, Connecticut 06510 Alain Mauviel Departments of Dermatology and Cutaneous Biology, and Bio- chemistry and Molecular Biology, Jefferson Medical College, and Section of Molecular Dermatology, Jefferson Institute of Molecular Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania 19107 R. L. McCallion School of Biological Sciences, University of Manchester, Manches- ter M13 9PT, England James B. McCarthy Department of Laboratory Medicine and Pathology, Biomedi- cal Engineering Center, University of Minnesota, Minneapolis, Minnesota 55455 John McGrath Departments of Dermatology and Cutaneous Biology, and Bio- chemistry and Molecular Biology, Jefferson Medical College, and Section of Molecular Dermatology, Jefferson Institute of Molecular Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania 19107 Paolo Mignatti Department of Genetics and Microbiology, University of Pavia, 27100 Pavia, Italy Contributors vii Lillian B. Nanney Departments of Plastic Surgery, Cell Biology, and Dermatology, Vanderbilt University Medical Center, Department of Veteran's Affairs, Nashville, Tennessee 37232-2631 William C. Parks Division of Dermatology, Department of Medicine, Washington University School of Medicine at the Jewish Hospital, St. Louis, Missouri 63110 David W. H. Riches Division of Basic Sciences, Department of Pediatrics, National Jewish Center for Immunology and Respiratory Medicine, Denver, Colorado 80206 Daniel B. Rifkin Department of Cell Biology and Kaplan Cancer Center, New York University Medical Center, New York, New York 10016-6402 Anita B. Roberts Laboratory of Chemoprevention, National Cancer Institute, Be- thesda, Maryland 20892-5055 Anne M. Romanic Department of Pathology, Yale University School of Medicine, New Haven, Connecticut 06510 Sabita Sankar Department of Pathology, Yale University School of Medicine, New Haven, Connecticut 06510 Michael B. Sporn Laboratory of Chemoprevention, National Cancer Institute, Be- thesda, Maryland 20892-5055 Jouni Uitto Departments of Dermatology and Cutaneous Biology, and Biochemistry and Molecular Biology, Jefferson Medical College, and Section of Molecular Dermatology, Jefferson Institute of Molecular Medicine, Thomas Jefferson Uni- versity, Philadelphia, Pennsylvania 19107 Howard G. Welgus Division of Dermatology, Department of Medicine, Washington University School of Medicine at the Jewish Hospital, St. Louis, Missouri 63110 Bengt Westermark Department of Pathology, University Hospital, S-751 85 Upp- sala, Sweden David T. Woodley Department of Dermatology, Northwestem University, Chicago, IIlinois 60611-3008 Kenneth M. Yamada Laboratory of Developmental Biology, National Institute of Dental Research, National Institutes of Health, Bethesda, Maryland 20892-4370 Preface It has been a great pleasure to write chapters and work with the other authors on the second edition of The Molecular and Cellular Biology o/Wound Repair. The book has been totally revised with all chapters rewritten. Several chapters in the first edition explored inflarnmation. These chapters have been deleted, since other books compre- hensively cover this topic. The deletions provided room to add Chapter 2 on the provisional matrix proteins, to expand Chapters 5 through 8 on growth factors, to add Chapter 9 on integrins, and to add Chapter 18 on scarring and nonscarring wound repair. As with the first edition, I have gained an immense knowledge about the molecu- lar and cellular biology of wound repair from my participation in the production of this book. The book has become a bridge between the basic sciences and the bedside, rather than a detailed treatise on molecular and cellular biology or a comprehensive review of animal and clinical wound studies. Thus, basic scientists who wish to determine wheth-. er their scientific endeavors might have applications in wound healing will find this volume valuable. On the other hand, clinical scientists will find that this volume gives a good scientific foundation for their clinical work. Chapter 1 gives an overview of processes involved in cutaneous wound repair. The initial version of this overview was published 10 years aga in the Journal 0/ the American Academy 0/ Dermatology and has undergone many revisions for reviews in journals and book chapters, including the first edition of The Molecular and Cellular Biology 0/ Wound Repair. This overview has once again been revised to include the highlights of data available up to and including the beginning of 1995. In Chapter 2, Kenneth Yarnada and I took on the formidable task of relating the molecular structure and function of provisional matrix proteins, such as fibrinogen, fibronectin, vitro- nectrin, thrombospondin, and tenascin, to their potential activities in wound repair. In Chapter 3, David Riches comprehensively reviews the macrophage with emphasis on lineage and phenotype modulation and how the different macrophage phenotypes might affect wound healing. In Chapter 4, Chris Haslett and Peter Henson exarnine how inflammation is resolved, not only in soft tissue repair, but in inflarnmatory processes in general. Prograrnmed cell death is a key phenomenon in this resolution. The growth factor section of the book gives the reader a comprehensive survey of the epidermal growth factor (EGF), fibroblast growth factor (FGF), platelet-derived growth factor (PDGF), and transforming growth factor-ß (TGF-ß) families and how these many diverse factors may interact in wound repair. Specifically, in Chapter 5, Lillian Nanney and Lloyd King review the seminal work of Stanley Cohn in discover- ix x Preface ing and characterizing epidermal growth factor, which led to his Nobel prize. Further- more, they outline the ever-expanding second messenger pathways that transmit the extracellular ligand-receptor signals into the nucleus and they allude to the many studies that have been done with EGF on animals and in the clinic. In Chapter 6, Judy Abraham and Michael Klagsbrun produced a comprehensive treatise on the FGF fami- ly, including molecular biology and biochemistry of the nine family members and an in-depth review of wound healing responses to these factors in animal and clinical studies. In Chapter 7, Carl-Henrik HeIdin and Bengt Westermark have written an excellent treatise on platelet-derived growth factors, explaining how the different PDGF isoforms can elicit diverse activities in cells by stimulating different receptor pairs. Last but not least, in Chapter 8, Anita Roberts and Michael Sporn have written an in-depth analysis of the mammalian TGF-ß isoforms from their molecular biology and structure to their use in animal and clinical studies. Transgenic mouse studies are beginning to elucidate the precise activities and necessities of many of these growth factor molecules. The third section of the book, entitled "New Tissue Formation: The Cutaneous Paradigm," begins with a review, in Chapter 9, of molecular and structural biology of integrin extracellular matrix receptors and how these receptors are expressed and potentially act during the wound repair process, with particular emphasis on reepi- thelialization. In Chapter 10, David Woodley continues with a discussion ofthe biology of the keratinocyte in wound repair. In Chapter 11, J oe Madri and colleagues survey the current knowledge on angiogenesis and describe how angiogenesis is closely con- trolled by cytokines and extracellular matrix signals. In Chapter 12, Jim McCarthy and his colleagues describe how parenchymal cell motility during wound repair and other morphogenetic events might depend on extracellular receptors other than integrins. This chapter also alludes to important new information on the controls and assembly of the actin motor apparatus in motile cells. In Chapter 13, Alexis Desmouliere and Giulio Gabbiani regale us with descriptions of myofibroblast phenotypes and functions in wound repair and fibrocontractive diseases. The fourth and final section of the book, entitled "Essentials of Tissue Remodel- ing," includes chapters on proteases, extracellular matrix molecules, and scar forma- tion. In Chapter 14, Paolo Mignatti, Daniel Rifkin, Howard Welgus, and William Parks present a comprehensive review of the important proteases involved in wound repair, including plasminogen activators, plasmin, and the metalloproteinases. In Chapter 15, Richard Gallo and Mert Bernfield provide a review on proteoglycans and their expres- sion in cutaneous wound repair. In Chapter 16, Beate Eckes, Monique Aumailley, and Thomas Krieg summarize current knowledge about the extracellular matrix collagens and how these proteins assemble in wound repair to patch the injured tissue with ascar. In Chapter 17, Jouni Uitto, Alain Mauviel, and John McGrath survey the molecular genetics and structure of basement membrane proteins and the deficiencies in these proteins that lead to recurrent or nonhealing cutaneous wounds. These lessons of nature provide great insight into the homeostatic value of these proteins and their importance in tissue reconstruction after architecturally disruptive injury. In Chapter 18, R. L. McCallion and M. W. J. Ferguson describe repair without scarring in fetal tissue and Preface xi propose ways in which adult wound healing might be modified to prevent or at least reduce scarring. In composite, these chapters give the reader a fairly comprehensive view of the molecular and cellular biology of wound repair, in both normal and abnormal healing processes. In addition, several chapters suggest methods by which inadequate or sub- standard healing might be improved. Richard A. F. Clark Stony Brook, New York