Skin Diseases with Defects in Cytoskeleton, Cellular Junctions and ECM BS31004 PDF

Skin Diseases with Defects in Cytoskeleton, Cellular Junctions and ECM BS31004 Biochemistry and Cell Biology Ying Liu ([email protected])  Describe the structure and function of cytoskeleton molecules, cellular junctions and ECM in maintaining skin integrity...

Skin Diseases with Defects in Cytoskeleton, Cellular Junctions and ECM BS31004 Biochemistry and Cell Biology Ying Liu ([email protected])  Describe the structure and function of cytoskeleton molecules, cellular junctions and ECM in maintaining skin integrity Intended Explain the pathophysiological Learning mechanisms underlying skin diseases Outcomes Compare the clinical manifestations and disease progression of several skin diseases Evaluate current treatment and potential future therapies Skin, Cyto- Skin Structure and Function skeleton, Cytoskeleton Molecules Cellular Junction Importance of Cellular Junctions and ECM Importance of Extracellulr Review Matrix (ECM) Skin Overview Protects the body from physical trauma, prevent water loss Helps regulate body temperature Allows us to be aware of our surroundings through sensory receptors Synthesizes chemicals such as melanin and vitamin D  Skin: Epidermis Structure: outermost layer, multiple sub-layers Function: waterproof barrier, creating our skin tone  Skin: Epidermis EPIDERMIS: AT THE BOTTOM NEWLY MADE STRATIFIED IS A LAYER OF SKIN CELLS SQUAMOUS STEM CELLS BECOME EPITHELIUM FLATTENED AND HARDENED AS THEY PUSH TO THE SURFACE (KERATIN) THIS PREVENTS TOP LAYERS ARE WATER LOSS DEAD CELLS, EVENTUALLY SHED FROM THE SKIN SURFACE  Skin: Dermis Thick, inner layer of the skin Made of loose fibrous connective tissue Contains elastic and collagen fibers Contains blood vessels, many sensory receptors, and glands Blood vessels help regulate body temperature Skin: Dermis Provides strength, elasticity, and nutrients to the skin Support body temperature regulation Provides sensation Papillary layer: loosely arranged collagen fibers, gives your fingerprint Reticular layer: densely woven collagen and elastic fibres, cushion from stress and strain  Skin: Hypodermis Hypodermis/Subcutaneous (Sub Q) layer Fat and connective tissue Insulation and cushioning Energy storage Anchoring skin to the underlying structures, allowing flexibility and movement Cellular Junctions Review Cellular Junctions Important for Skin Tight junctions: Desmosomes: Adherens seal the space essential for junctions: between adjacent mechanical maintain cell cells strength positioning and support wound healing Gap junctions: Hemidesmosomes channels : anchor the basal layer of epidermis  ECM in the Skin Collagen: provides tensile strength and resilience Elastin: provides elasticity and flexibility Proteoglycans: hyaluronic acids, hydrates the skin by binding to water Fibronectin: cell adhesion, migration and migration Integrin: fibronectin receptor, anchors skin cells  EB Overview EB Simplex Epidermolysis Junctional EB Bullosa (EB) Dystrophic EB  EB Overview Epidermolysis Bullosa (EB) is a group of genetics disorders Signs and symptoms: blistering in response to minor trauma Types of EB: mutations in different proteins such as keratins, collagens and laminins EB Simplex Epidermolysis Bullosa (EB) simplex is the most common and mildest forms of EB Mutations: keratin genes (KRT 5 and KRT 14) Mutant proteins -> increased fragility - > blister formation (accumulation of fluid in extracellular space)  EB Simplex 1 2 3 Keratins: form heterodimers Connect to desmosomes and Protect skin cells from that assemble into larger hemidesmosomes to anchor environmental damages filament structures cells to each other and to ECM, respectively  Junctional EB Blisters over large Usually starts from area of the body birth or infancy Affected children Affecting skin and susceptible for mucous membrane infections and malnutrition Mutations in subunits Both are involved in of Laminin 332 (a anchoring epidermis trimer) and Collagen to the basement 17 membrane Junctional EB  Dystrophic EB Blisters and scar formation Increased risk of skin cancer Mutations in Collagen 7 (Anchoring fibrils) involved in anchoring the epidermis to the dermis Plays a key role in maintaining structural integrity of the skin Also plays a role in cell signaling and would healing  Wound Care Treatment and Therapy Infection Prevention for EB Cell and Gene Therapy Wound Care Infection Prevention Regular cleaning of wound sites Topical creams Antibiotics (topical or systemic) Cell and Gene Therapy CRISPR-Cas 9 based gene editing to Gene therapy: correct or replace mutated genes Viral vector delivered normal genes LAMA 3 for JEB Genes: COL7A1 for DEB (EB-101, Abeona Therapeutics) Stem cell therapy Cell Therapy: Skin graft Cell and Gene Therapy