EXTRACELLULAR MATRIX

SRY SURYANI WIJAYA

EXTRACELLULAR MATRIX
(ECM)
Referred as Connective Tissue
ECM contains 3 major classes of
biomolecules:
Structural proteins : collagen,elastin,fibrillin
Specialized proteins :
fibrillin,fibronectin,laminin
Proteoglycans : Glycosaminoglycans (GAGs)
ECM plays important roles in
development,inflammatory states,spread of
cencer cells.

Collagen
Major component of most connective tissue
Constitutes approximates 25 % of the
protein of mammal.
Collagen type I
- All collagens triple helical structure.
- Glycine residues at every third position
of triple helical portion of the chain.
-Gly-X-Y absolute requirement for the
formation of triple helix.

 X proline
confer
rigidity on
Y hydroxyproline collagen molecule.
Collagen fibers : stabilized by the
formation of covalent-cross link,both
within and between the triple helical
units. (through the action of lysyl
oxidase).
Important for the tensile
strength of fibers.

 Types of collagen and their

genes.
Classification of collagens,based
on the structure they form.

Synthesis of collagen
Newly synthesized collagen
extreme post translational
modification before becoming part of
a mature extracellular collagen fibers.
Collagen syntesized in ribosome
precursor preprocollagen
cleavage of signal peptide
hydroxylation of prolyl residues and
some lysyl residues.Glycosylation of
some hydroxylysyl residues.
Formation of triple helix secretion
to ECM

 Collagen relatively stable.

Break down (high) during
starvation,inflammatory.
Genetic diseases from abnormalities in
the synthesis of collagen.
Scurvy def vit C affects structure of
collagen.
Major signs bleeding gums,subcutaneus
hemorr,poor wound healing.

Elastin
Responsible for extensibility & elastic
recoil in tissues.
Eg : lung,large Arterial blood
vessels,some elastic ligaments ( large
amount)
Skin,ear cartilage ( smaller amounts)

Williams syndrome
Deletions in the elastin gene.
Developmental disorder affecting tissue and
connective tissue,CNS
Supravalvular aortic stenosis.

 Scleroderma
accumulation of
elastin
Fragmentation /elastin
pulmonary emphysema,aging of the
skin and cutis laxa.
Major difference between
collagen and elastin

Fibrillin
Large glycoproten 350 kDa.
Structural component of microfibril.
Mutations in the gen for fibrillin:
Marfan syndrome :

Inherited disease.
Autosomal dominant
Affect eyes (dislocation of lens)
Skeletal system
tall,arachnodactyly,hyperextensibility of the
joints.

 Cardiovascular system
Mutations in the gene (chromosome 15)

Fibronectin
Major comp of ECM
Aalso found in soluble form in plasma.
Involved in cell adhesion and migration.

Laminin
Major prot comp of renal glomerulus & other
basal lamina.

 Proteoglycans & Glycosaminoglycans.

There are at least 7 GAGs:
Ha,cs,ks I & II,heparin,heparan sulfat,dermatan
sulfat.

Mucopolysaccharidoses
Inborn error of metabolisme
Def of enzyme that degrade GAGs

Mucolipidosis
combine features of
mucopolysaccharidase & spongiolipidosis

Proteoglycans and GAGs

Hyaluronic acid
Play an important role in permiting cell migration
during morphogenesis and wound repair.

Chondroitin sulfates
Maintain shape
Located at sites of calcification in endothelial
bone,cartilage

Keratan sulfate I & dermatan sulfate

Present in cornea
Also in cartilage.

 Heparin
An important anticoagulant
Binds with factors IX & XI,but its most
important interaction with antithrombin III.

Function of GAGs and

proteoglycans.

Bone mineralization
Bone is a mineralized connective tissue
disease.
Contain organic and inorganic material.
Principal protein : type I collagen (90-95
% of the organic material).
Type V collagen :small amount.

Inorganic material : hydroxypaptite,

sodium,magnesium,carbonate,fluoride.

 99 % bodys calsium is contained in

bone.
Bone
dynamic structure,remodeling
(osteoblast and osteoclast)
adapt to
both physical and hormonal signals.
Osteoclasts
Multinucleated cells derived fr pluripotent
hematopoetic stem cells.
Bone resorption

 Osteoblast
Mononuclear cells derived fr pluripotent
mesenchymal precursor.
Synthesized most of the proteins found in
bone,growth factors and cytokines
Deposition of new bone matrix
Controlled mineralization : regulation
passage of calsium and phosphate ion
across surface membrane.

 Regulations of bone metabolism

Stimulate osteoblast : parathyroid
hormone
Inhibit : steroid hormone.
Stimulate osteoclast : parathyroid
hormone
Inhibit : calcitonin and estrogen.

 Metabolic & genetic disorders involve

bone.
Osteogenesis imperfecta.
Brittle bone,thin sclera and translucent,may appear
blue (owing to def of connective tissue ).
Mild,extensive,severe and variable.
Extensive : occur in the new born
90 % mutations in COL1A1 and COL1A2
genes,encoding pro1(I) and pro2(I) chains.

 Osteopetrosis
Marble bone disease
Increased bone density (inability to resorb
bone)
Mutation in the gene (8q22)
Carbonic anhdrase II
def
normal bone
resorption does not occur.

 Osteoporosis
Generalized progressive reduction in
bone mass tissue per unit volume
causing skeletal weakness
Fracture occur easily.
Estrogen and interkleukin-1.

 Chondrodysplasia
Mixed group of hereditary disorders affecting
cartilage.
Short limbed dwarfism and numerous skeletal
deformities.
Mutations in COL2A1 gene
abn collagen type II
Stickler syndrome (deg of joint cart and vitreous body
of the eye).
The best known of chondrodysplasia is
ACHONDROPLASIA
inherited,autosomal
dominant,new mutation.
Achondrodysplasia is not a collagen disorder but due
to mutation of gene encoding FGR3 .

 FGR3 : affect the growth of

differentiation of cells of
mesenchymal and neuroectodermal
origin.