Page 74 - Concise Pathology for Exam Preparation ( PDFDrive )

3 Healing and Repair 59

3. Receptors lacking intrinsic tyrosine kinase activity
Receptors can transmit extracellular signals to nucleus by activating Janus kinases
(JAKs) which activate cytoplasmic transcription factors STATs (signal transducers
and activators of transcription), which in turn enter the nucleus and activate gene
transcription.
Examples: Receptors for cytokines like IL-2, IL-3, interferons, granulocyte monocyte-
colony stimulating factor (GM-CSF) and growth hormone.
Note: All ligands do not induce stimulatory signals, growth inhibitory signals are also
generated, eg, TGF-b binding with its receptor phosphorylates some intracellu-
lar proteins, which in turn increase the synthesis of CDK inhibitors and block the
activity of transcription factors and cell cycle progression.
4. Nuclear receptors
Lipid soluble ligands (steroid hormones, thyroid hormone, vitamin D and retinoids)
can diffuse into the cell to interact with intracellular proteins forming a receptor–
ligand complex which in turn binds to the inactive receptor located in the nucleus to
activate it. Activated receptor binds to the specific DNA sequences known as
hormone response elements on target genes or transcription factor.
Example: A group of receptors called peroxisome proliferator-activated receptors
(PPARs) involved in inflammation and atherosclerosis.

Q. Write briefly on extracellular matrix (ECM) and cell-matrix
interactions.
Ans. Tissue repair depends on
1. Growth factor activity
2. Interaction between cells and ECM components
ECM is a constantly changing macromolecular complex, which assembles into a network
that surrounds and supports the cells. It has the following functions:

1. Provides support and anchorage for cells, segregates tissues from one another and
regulates intercellular communication.
2. Sequesters growth factors and serves as a reservoir for them (FGF and HGF; allows
rapid deployment of growth factors after injury for regeneration).
3. Provides a substrate for cell adhesion.
4. Sequesters water to provide turgor to soft tissues.
5. Sequesters minerals to provide rigidity to bone.
6. Regulates proliferation and controls cell growth, movement and differentiation
(by signalling through cellular receptors of integrin family).

ECM Exists in Two Different Forms
1. Interstitial matrix: Synthesized by mesenchymal cells, this randomly fills up the space
between cells and supporting vascular and smooth muscle structures.
2. Basement membrane: The interstitial matrix organizes itself around epithelial,
endothelial and smooth muscle cells to form a meshwork, which anchors down
the above cells to loose connective tissue underneath. This meshwork is called
‘basement membrane’. Its major components are amorphous nonfibrillar type
IV collagen and laminin.

Components of ECM
• Fibrous structural proteins such as collagens and elastins for tensile strength and
recoil
• Water hydrated gels such as proteoglycans and hyaluronate for resilience and lubrication
• Adhesive glycoproteins that connect the matrix elements to one another and to cells

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