The document defines and discusses the extracellular matrix (ECM). It notes that the ECM provides structural and biochemical support to surrounding cells and includes interstitial matrix and basement membrane. The ECM is composed of proteoglycans, non-proteoglycan polysaccharides, fibres, and other components that form an interlocking mesh. The ECM serves functions like tissue growth and healing, cell culture support, and injury repair.

1. PRESENTED BY:
SYED KASHIF
DEPARTMENT OF PHARMACOLOGY
AACP
EXTRACELLULAR MATRIX
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2. CONTENTS
 DEFINITION
 ROLE AND IMPORTANCE
 MOLECULAR COMPONENTS
1.PROTEOGLYCANS
2.NONPROTEOGLYCANS
3.FIBRES
4.OTHER COMPONENTS
 FUNCTIONS
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3. 3

4. DEFINITION
 ECM is a collection of extracellular components
secreted by cells that provides structural &
biochemical support to the surrounding cells
 It mainly includes interstitial matrix & the basement
membrane
 The interstitial matrix contains gels of
polysaccharides & fibrous proteins
 Basement membranes are sheet-like depositions
of ECM on which various epithelial cells rest.
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5. ROLE & IMPORTANCE
 ECM can serve many functions, such as providing
support, segregating tissues from one another, and
regulating intercellular communication
 In addition, it sequesters a wide range of cellular growth
factors and acts as a local store for them. Changes in
physiological conditions can trigger protease activities
that cause local release of such store
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6. MOLECULAR COMPONENTS
 Components of the ECM are produced
intracellularly by resident cells and secreted into the
ECM via exocytosis. Once secreted, they then
aggregate with the existing matrix. The ECM is
composed of an interlocking mesh of
fibrous proteins and glycosaminoglycans (GAGs).
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7. PROTEOGLYCANS
 Glycosamines are carbohydrate polymers usually
attached to extracellular matrix proteins to
form proteoglycans(hyaluronic acid is a notable
exception)
 Proteoglycans have a net negative charge that
attracts positively charged sodium ions (Na+), which
attracts water molecules via osmosis, keeping the
ECM and resident cells hydrated. Proteoglycans
may also help to trap and store growth
factors within the ECM.
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9. TYPES OF PROTEOGLYCANS
 Heparin sulfate:Heparan sulfate (HS) is a
linear polysaccharide found in all animal tissues. It
occurs as a proteoglycan (PG) in which two or three
HS chains are attached in close proximity to cell
surface or ECM proteins.[ It is in this form that HS
binds to a variety of protein ligands and regulates a
wide variety of biological activities,
including developmental
processes,angiogenesis, blood coagulation, and
tumour metastasis.
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11.  Chondrotoin sulfates: Chondroitin sulfate is a
sulfated glycosaminoglycan (GAG) composed of a
chain of alternating sugars (N-acetylgalactosamine
and glucuronic acid). It is usually found attached to
proteins as part of a proteoglycan
 chondrotoin sulfates contribute to the tensile
strength of cartilage, tendons, ligaments, and walls
of the aorta. They have also been known to
affect neuroplasticity.
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13.  Keratan sulfate: Keratan sulfate (KS), also called
keratosulfate, is any of several sulfated
glycosaminoglycans (structural carbohydrates) that
have been found especially in the cornea, cartilage,
and bone
 Keratan sulfates have a variable sulfate content
and, unlike many other GAGs, do not contain uronic
acid. They are present in the cornea,
cartilage, bones, and the horns of animals.
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14. 14

15. NON-PROTEOGLYCAN POLYSACCHARIDE
 Hyaluronic acid
 Hyaluronic acid (or "hyaluronan") is
a polysaccharide consisting of alternating residues of D-
glucuronic acid and N-acetylglucosamine, and unlike other
GAGs, is not found as a proteoglycan. Hyaluronic acid in the
extracellular space confers upon tissues the ability to resist
compression by providing a counteracting turgor (swelling)
force by absorbing significant amounts of water. Hyaluronic
acid is thus found in abundance in the ECM of load-bearing
joints. It is also a chief component of the interstitial gel.
Hyaluronic acid is found on the inner surface of the cell
membrane and is translocated out of the cell during
biosynthesis.[16]
 Hyaluronic acid acts as an environmental cue that regulates
cell behavior during embryonic development, healing
processes, inflammation, and tumor development. It interacts
with a specific transmembrane receptor
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16. 16

17. FIBRES
 Collagen
 Collagens are the most abundant protein in the
ECM. In fact, collagen is the most abundant protein
in the human body[18][19]and accounts for 90% of
bone matrix protein content.[20] Collagens are
present in the ECM as fibrillar proteins and give
structural support to resident cells. Collagen is
exocytosed in precursor form (procollagen), which
is then cleaved by procollagen proteases to allow
extracellular assembly. Disorders such as Ehlers
Danlos Syndrome, osteogenesis imperfecta,
and epidermolysis bullosa are linked with genetic
defects in collagen-encoding genes. 17

18.  The collagen can be divided into several families
according to the types of structure they form:
 Fibrillar (Type I, II, III, V, XI)
 Facit (Type IX, XII, XIV)
 Short chain (Type VIII, X)
 Basement membrane (Type IV)
 Other (Type VI, VII, XIII)
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20.  Elastin:Elastins, in contrast to collagens, give elasticity
to tissues, allowing them to stretch when needed and
then return to their original state. This is useful in blood
vessels, the lungs, in skin, and the ligamentum nuchae,
and these tissues contain high amounts of elastins.
Elastins are synthesized by fibroblasts and smooth
muscle cells. Elastins are highly insoluble,
andtropoelastins are secreted inside a chaperone
molecule, which releases the precursor molecule upon
contact with a fiber of mature elastin. Tropoelastins are
then deaminated to become incorporated into the elastin
strand. Disorders such as cutis laxa and Williams
syndrome are associated with deficient or absent elastin
fibers in the ECM
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21. 21

22.  Fibronectin
 Fibronectins are glycoproteins that connect cells with
collagen fibers in the ECM, allowing cells to move
through the ECM. Fibronectins bind collagen and cell-
surface integrins, causing a reorganization of the
cell's cytoskeleton and facilitating cell movement.
Fibronectins are secreted by cells in an unfolded,
inactive form. Binding to integrins unfolds fibronectin
molecules, allowing them to form dimers so that they
can function properly. Fibronectins also help at the site
of tissue injury by binding to platelets during blood
clotting and facilitating cell movement to the affected
area during wound healing.
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24.  Laminin
 Laminins are proteins found in the basal laminae of
virtually all animals. Rather than forming collagen-
like fibers, laminins form networks of web-like
structures that resist tensile forces in the basal
lamina. They also assist in cell adhesion. Laminins
bind other ECM components such as collagens,
nidogens, and entactins
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25. 25

26. FUNCTIONS
 Ecm is responsible for growth & healing of tissues
 It is currently being used regularly to treat ulcers by
closing the hole in the tissue that lines the stomach
 Extracellular matrix proteins are commonly used in
cell culture systems to maintain stem and precursor
cells in an undifferentiated state during cell culture
and function to induce differentiation of epithelial,
endothelial and smooth muscle cells in vitro.
Extracellular matrix proteins can also be used to
support 3D cell culture in vitro for modelling tumor
development.
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27.  . In terms of injury repair and tissue engineering,
the extracellular matrix serves two main purposes.
First, it prevents the immune system from triggering
from the injury and responding with inflammation
and scar tissue. Next, it facilitates the surrounding
cells to repair the tissue instead of forming scar
tissue
 Extracellular matrix coming from pig small intestine
submucosa are being used to repair "atrial septal
defects" (ASD),
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28. SUMMARY
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29. CELL SIGNALLING:COMMUNICATION BETWEEN
CELLS & THEIR ENVIRONMENT
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30. CONTENTS
1) DEFINITION
2) CLASSIFICATION
3) Signalling molecules
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31. WHAT IS CELL SIGNALING
 Cell signaling is a process of a cell responding to a
stimulus from its environment by relaying its
information into internal compartment from its
surface
 The ability of cells to perceive and correctly
respond to their microenvironment is the basis of
cell signaling
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32. CLASSIFICATION
A)Extra cellular signaling or chemical signaling
I. Intracrine
II. Autocrine
III. Juxtacrine
IV. Pancrine
V. endocrine
B)Cell”s direct signaling or intracellular signalling
I. Receptors
II. Cell surface protiens
III. Gap junctions 32

33.  Intracrine signals are produced by the target
cell that stay within the target cell.
 Autocrine signals are produced by the target
cell, are secreted, and affect the target cell
itself via receptors. Sometimes autocrine
cells can target cells close by if they are the
same type of cell as the emitting cell. An
example of this are immune cells.
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CLASSIFICATION

34.  Juxtacrine signals target adjacent (touching) cells.
These signals are transmitted along cell
membranes via protein or lipid components integral
to the membrane and are capable of affecting either
the emitting cell or cells immediately adjacent.
 Paracrine signals target cells in the vicinity of the
emitting cell. Neurotransmittersrepresent an
example.
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35.  Endocrine signals target distant cells. Endocrine
cells produce hormones that travel through
the blood to reach all parts of the body.
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36. 36

37. SIGNAL TYPE SIGNAL PRODUCED
AT
SIGNAL TARGETED
AT
INTRACRINE CELLS SAME CELLS
AUTOCRINE CELLS SAME CELLS BUT
VIA RECEPTORS
JUXTACRINE CELLS ADJACENT CELLS
PARACRINE CELLS CELLS IN VICINITY
ENDOCRINE CELLS DISTANT CELLS 37
SUMMARY

38. DIRECT CONTACT SIGNALLING
1. RECEPTORS
2. G-PROTEIN COUPLED RECEPTORS
3. GAP JUNCTIONS
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39. RECEPTORS
 RECEPTORS are proteinaceous structures present
either on cell surface or inside the cell
 In case of membrane bound receptors
signals(ligands) bind to these receptors activates
them & produce a cascade of intracellular signals
that alter the cell
 In case of intracellular receptors the ligand enters
inside the cell & brings about activation of the
receptors
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40. DIRECT CONTACT SIGNALING
 GAP JUNCTIONS
 These are specialised cell-cell junctions that are
formed between closely opposed plasma
membranes & directly connect the cytoplasms of
the joined cells via narrow water filled channels
 These channels allow the exchange of small
intracellular signalling molecules such as Ca &
cAMP
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41. CELL SURFACE RECEPTORS
 Al l water soluble signal molecules act by binding to
specific receptor proteins present on the target cells
. Hence cell surface proteins are oftenly termed as
signal transducers
 There are mainly 3 types of cell surface receptors
1. Ion-channel linked receptors
2. G-protein coupled receptors
3. Enzyme-linked receptors
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42. ION-CHANNEL LINKED RECEPTORS
 Also known as TRANSMITTER-GATED ION
CHANNELS or IONOTROPIC RECEPTORS
 They are involved in rapid synaptic signaling
between electrically excitable cells
 This type of signaling is mediated by
neurotransmiters that transiently open or close the
ion channels formed by the proteins to which they
bind thus changing the ion permeability of the
plasma membrane & excitability of post synaptic
cell
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43. G-PROTEIN COUPLED RECEPTORS
 These receptors act indirectly to regulate the
activity of membrane bound protein(ion channel or
enzyme)
 The interaction between the receptor & the
signaling is mediated by a third protein called as
GTP BINDING PROTEIN(G protein)
 The activation of the target protein can change the
concentration of the mediators (in case of
enzymes) or change the membrane permeability(in
case of ion channels)
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44. ENZYME LINKED RECEPTORS
 These when activated either function directly as
enzymes or are associated with the enzymes they
activate
 These are formed by single pass transmembrane
proteins that have their ligand binding site outside
the membrane & enzyme binding site inside the
membrane
 The majority of these kind of receptors are either
protein kinases or associated with them & bring
about phosphorylation
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45. SIGNALING MOLECULES
 Signaling molecules interact with target cell as
a ligand to cell surface receptors & elicit cell
signalling
 This generally results in the activation of second
messengers, leading to various physiological
effects
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 There are 3 important classes of signalling
molecules
 :
 Hormones are the major signaling molecules of
the endocrine system, though they often regulate
each other's secretion via local signaling (e.g. islet
of Langerhans cells), and most are also expressed
in tissues for local purposes (e.g. angiotensin) or
failing that,structurally related molecules are

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48.  Neurotransmitters are signaling molecules of
the nervous system, also
includingneuropeptides and neuromodulators.
Neurotransmitters like the catecholamines are also
secreted by the endocrine system into the systemic
circulation.
 Ex: Ach
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Cytokines are signaling molecules of
the immune system, with a primary
paracrine or juxtacrine role, though they
can during significant immune responses
have a strong presence in the circulation,
with systemic effect (altering iron
metabolism or body temperature). Growth
factors can be considered as cytokines or a
different class

50. THANK YOU
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