Table Of ContentBiology of Extracellular Matrix:
A Series
Editor
ROBERT P. MECHAM
A list of books in this series is available from the publisher on request.
REGULATION OF MATRIX
ACCUMULATION
ROBERT P. MECHAM
Edited by
Pulmonary Disease and Critical Care Division
Department of Cell Biology and Physiology
Washington University School of Medicine
Jewish Hospital
St. Louis, Missouri
1986
ACADEMIC PRESS, INC.
Harcourt Brace Jovanovich, Publishers
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COPYRIGHT © 1986 BY ACADEMIC PRESS. INC
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ACADEMIC PRESS, INC.
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United Kingdom Edition published by
ACADEMIC PRESS INC. (LONDON) LTD.
24-28 Oval Road, London NWI 7DX
Library of Congress Cataloging in Publication Data
Regulation of matrix accumulation.
(Biology of extracellular matrix)
Bibliography: p.
Includes index.
1. Ground substance (Anatomy) 2. Cellular control
mechanisms. 3. Collagen—Metabolism. 4. Connective
tissues. I. Mecham, Robert P. II. Series.
QP88.23.R44 1986 611'.0182 86-3418
ISBN 0-12-487425-8 (alk. paper)
PRINTED IN THE UNITED STATES OF AMERICA
86 87 88 89 9 8 7 6 5 4 3 2 1
Contributors
Numbers in parentheses indicate the pages on which the authors' contributions begin.
RICHARD A. BERG, Department of Biochemistry, University of Medicine
and Dentistry, Rutgers Medical School, Piscataway, New Jersey
08854 (29)
JOSEPH G. BIETH, INSERM Unite 237, Faculte de Pharmacie, Universite
Louis Pasteur, 67048 Strasbourg Cedex, France (217)
JOACHIM BOHM, Max-Planck-Institut fur Biochemie, 8033 Martinsried,
Federal Republic of Germany (99)
KENNETH R. CUTRONEO, Department of Biochemistry, College of Medi
cine, University of Vermont, Burlington, Vermont 05405 (119)
JEFFREY M. DAVIDSON,1 Department of Pathology, University of Utah
School of Medicine, and Research Service, Veterans Administra
tion Medical Center, Salt Lake City, Utah 84148 (177)
M. GABRIELLA GIRO,2 Department of Pathology, University of Utah
School of Medicine, and Research Service, Veterans Administra
tion Medical Center, Salt Lake City, Utah 84148 (177)
1 Present address: Department of Pathology, Vanderbilt University School of Medi
cine, and Research Service, Veterans Administration Medical Center, Nashville, Ten
nessee 37203.
2 Permanent address: Istituto di Istologia-Embriologia, Universita di Padova, 35100
Padova, Italy.
ix
χ CONTRIBUTORS
JOHN J. JEFFREY, Division of Dermatology, Departments of Medicine and
Biological Chemistry, Washington University School of Medicine,
St. Louis, Missouri 63110 (53)
HERBERT M. KAGAN, Department of Biochemistry, Boston University
School of Medicine, Boston, Massachusetts 02118 (321)
THOMAS KRIEG, Dermatologische Klinik, Ludwig-Maximilians-Univer-
sitat, 8000 Munchen, Federal Republic of Germany (99)
PETER K. MULLER, Max-Planck-Institut fur Biochemie, 8033 Mar-
tinsried, Federal Republic of Germany (99)
ANDREAS G. NERLICH, Max-Planck-Institut fur Biochemie, 8033 Mar-
tinsried, Federal Republic of Germany (99)
S. M. PARTRIDGE, Millstream House, Cheddar, Somerset BS27 3N6,
England (1)
Luu PHAN-THAN, Max-Planck-Institut fur Biochemie, 8033 Martinsried,
Federal Republic of Germany (99)
SUSAN SHULL, Department of Biochemistry, College of Medicine, Univer
sity of Vermont, Burlington, Vermont 05405 (119)
BRIAN S. SPOONER, Division of Biology, Kansas State University, Man
hattan, Kansas 66506 (399)
KENNETH M. STERLING, JR.,3 DepartmentofBiochemistry, College of Med
icine, University of Vermont, Burlington, Vermont 05405 (119)
HOLLY A. THOMPSON-PLETSCHER, Department of Chemistry, University of
Montana, Missoula, Montana 59812 (399)
3 Present address: Division of Pediatric Gastroenterology, Mount Sinai School of Medi
cine, New York, New York 10029.
Preface
More than two decades have passed since the first publication of the
International Review of Connective Tissue Research. Under the editor
ship of Dr. David Hall, later joined by Dr. David Jackson, the series
has published timely reviews which highlight the tremendous develop
ments in connective tissue research. Moreover, the International Re
view has helped to encourage interactions between diverse disciplines,
a goal stated by Dr. Hall in the first preface.
With this volume, the International Review of Connective Tissue Re
search undergoes a change of editorship and, with this, major changes
in format. The most obvious format change is a new title: Biology of
Extracellular Matrix. The title was selected to emphasize the new
breadth of connective tissue studies; once limited principally to the
biochemical characterization of individual connective tissue compo
nents, the field has grown to include, indeed ordain, research on the
interactions between cells and extracellular maeromolecules.
A second, more substantial change in format is that most volumes in
the series will be devoted to a particular theme, rather than covering
diverse, unrelated subjects. To ensure that the volumes have cohesion
and appropriate editorial review, editors and co-editors will be selected
who are leaders in the various areas of study reviewed. For example,
Dr. Thomas Wight will be co-editor of the second volume of this series,
devoted to the biology of proteoglycans. Drs. Richard Mayne and
Robert Burgeson will edit the third volume, which will address the
genetic diversity of collagen, emphasizing the "new" collagen types
IV-X.
Another feature of the new series will be autobiographical reminis
cences from investigators who have greatly influenced our progress in
understanding extracellular matrix biology. This first volume of Biol
ogy of Extracellular Matrix opens with a personal retrospective by
Miles Partridge. Those who read the article surely will acquire a
keener appreciation for the creative insights that people like Dr. Par
tridge brought to the field.
xi
xii PREFACE
While most volumes of this series will explore specific subjects, we
expect to publish occasional collections that are not unified by a single
theme, believing that this practice will encourage new lines of re
search and new perspectives on basic knowledge not always conducive
to discussion in a rigidly topical survey. In some ways this first volume
might be viewed as such a collection. Although each review is appro
priate for the topic "Regulation of Matrix Accumulation," each also
draws attention to the possibilities of the subject when looked at in
new ways.
The article by Jeffrey presents an analysis of collagenolytic degrada
tion of extracellular collagen, but its larger purpose is to raise a more
fundamental question about the relationship between collagenolytic
proenzymes and enzyme-inhibitor complexes and the role of this rela
tionship in the regulation of collagen turnover. Similarly, Berg pro
poses that degradation of newly synthesized intracellular collagen pro
vides a tightly controlled mechanism for cells either to sort or to
modulate the amount of collagen which is available for extracellular
transport. Muller et al. hypothesize that degradation fragments of col
lagen have biological activity; specifically, that fragments of collagen
molecules liberated during extracellular processing of procollagen feed
back to the cell to alter specifically the collagen synthetic rate. This
feedback system may be an exquisite example of reciprocal interaction
between a cell and the macromolecules that it secretes to form a struc
turally intact matrix.
To view regulation of matrix accumulation by cells in isolation is
almost certainly to see the process too narrowly. Cutroneo et al. point
to the role of humoral factors as potent regulators. The broad dimen
sions of the subject are suggested by considering the varied responses
of the cell to multiple signals in the extracellular environment. The
inhibitory or stimulatory effects of steroid hormones on the synthesis
of matrix macromolecules may lead to altered composition or architec
ture of the extracellular matrix or result in abnormal biochemical
functions of cells.
The use of modern experimental techniques to answer difficult bio
logical questions is illustrated in the review of elastin by Davidson and
Giro. Elastin has been a difficult protein to study because of its un
usual biochemical and physical properties. Yet recent advances in mo
lecular and cellular biology and the application of useful model sys
tems have contributed greatly to understanding the synthesis,
deposition, and turnover of this unique protein.Equally detailed and
impressive information on elastin degradation is presented by Bieth.
Looking closely at the proteases that degrade elastin, Bieth seeks to
PREFACE xiii
define the circumstances under which a proteolytic enzyme can be
properly called an elastase. This analysis leads also to questions re
garding the relationships between elastase and proteolytic inhibitors
in serum and disease.
Accumulation of functional collagen or elastin in the extracellular
space necessitates an enzymatically catalyzed joining of individual
molecules to form a highly cross-linked polymer. Kagan addresses the
problem of forming an insoluble matrix from soluble macromolecules
in an analysis of the complex enzyme system that catalyzes cross-link
formation. Spooner and Thompson-Pletscher, in the final article in this
volume, summarize the important interrelationship between matrix
accumulation and the development of form. Spooner and Thompson-
Pletscher discuss how a wide variety of matrix components act as mor-
phogenetic substrates and as cues for cellular differentiation in
branching morphogenesis. As embryonic cells organize to form tissues
and organs, it is clear that matrix accumulation—which includes re
modeling as well as synthesis—is subject to direct regulation by the
reacting cells.
It is hoped that the Biology of Extracellular Matrix will serve to focus
current and future research in the biochemistry and cell biology of
extracellular matrix. This series cannot thrive without a large mea
sure of enthusiasm and active participation from contributors and
readers. Comments including suggestions of topics will be gratefully
received. Indeed, nothing could be more useful in this endeavor than to
know from those who are interested how they would have us proceed.
ROBERT P. MECHAM
Reflections on a Career in
Connective Tissue Research
S. M. Partridge
Somerset, England
Text 1
References 27
I was born in Whangarei, New Zealand, on August 2nd, 1913. My
father emigrated from Warwickshire, England, in 1912 and, among
rumours of the coming war joined the New Zealand army as a Sergeant
Instructor. My mother was born in Kent and joined him for marriage
in New Zealand soon after her nineteenth birthday. She had very
happy recollections of New Zealand, but unfortunately their time to
gether was short: my father was killed in action with the ANZAC
expeditionary force soon after the fateful landing at Gallipoli in April,
1915. Having little to keep her in New Zealand, my mother returned
with me to her parents' home in Dover.
My early schooling was supported by and conducted under the super
vision of the New Zealand High Commissioner's Office in London, but
at the end of the war this arrangement changed because my mother
married again. My stepfather was Lt. Charles McCarthy R.N.V.R., a
"Wireless Officer" posted with the mine-sweeping trawlers of the
Dover Patrol. As soon as the war was over and he was demobilized, my
stepfather joined with two ex-naval colleagues to establish a business
in London. This was still in existence when he died in 1952 but under
went all sorts of varying fortunes in the meantime. As it was, my
mother was needed to help establish the new business, and at the age
of seven I went to live with my grandmother who had retired to live
near her family in a country cottage in the village of Heckington in
Lincolnshire.
I lived in the village until the age of twelve, and still have happy
memories of what seems like an almost idyllic experience, moving
freely around the various farms occupied by my grandmother's family,
and witnessing the interesting operations of the wheelwright, the
1
REGULATION OF MATRIX ACCUMULATION Copyright © 1986 by Academic Press, Inc.
All rights of reproduction in any form reserved.
2 S. Μ. PARTRIDGE
S. Μ. PARTRIDGE
blacksmith, the saddler and half-a-dozen other tradesmen, some prac
tising trades that are no longer pursued: My formal education, how
ever, was very attenuated: I attended the two-roomed village school,
where the pace was necessarily set by the slowest learners.
Inevitably this had to come to an end and I rejoined my parents in a
London suburb, this decision being taken mainly, I believe, because of
the necessity of finding a good school. This proved successful, and with
a good recommendation from my village school master I was accepted
by a school of "grammar school" standing in West London. However, I
