Collagen as a dermal component play a significant role in ultrastructure and function of skin

1. STRUCTURE,FUNCTION, SYNTHESIS
AND APLLIED ASPECTS
Dr. RANJAN DASH

2. GRADUAL SENESCENCE
WITH TIME

3. BEAUTY IS SKIN DEEP

4. BETTER TO HOPE THAN DESPAIR

5. What is collagen ?
 A fibrous protein
 Most abundant
protein in human
body(25-30% of total
protein content)
 Forms major part of
extracellular matrix
and connective
tissues like dermis of
skin cornea bones,
tendons, cartilage,
and vessels
 Forms 80% of dry wt.
of dermis

6. Collagen In Various Tissues Other Than Skin

7. CLASSIFICATION OF COLLAGEN
 Atleast 28 types of Collagen coded by 42 different genes.
such as Collagens I, II,III,IV,V,VI,VII………..XXVII,XXVIII .
TYPES CODING GENES
I COL1A1,COL1A2
II COL2A1
III COL3A1
IV COL4A1,COL4A2,COL4A3
COL4A4,COL4A5,COL4A6
. .
. .
XXVIII COL28A1
 As per their length and number of collagenous and non-collagenous domain
and architectural contribution in various tissues ,four different classes of
collagens.

8. MAJOR CLASSES OF COLLAGEN
 FIBRILLAR : I ,II ,III ,V , XI , XXIV and XXVII
 NETWORK FORMING : IV , VIII , X
 TRANSMEMBRANE : XXIII , XXVII
 ANCHORING FIBRIL : VII

9. STRUCTURE OF COLLAGEN
A compact triple helix : 3 alpha chains coiled
around each other to form rod-like structure of
dimension 1.5 * 300 nm
Type1collagen is the prototype (alpha1)2 alpha2
The triple helix is largely explained by the unusual
amino- acids composition such as Proline ,
Hydroxyproline
Each alpha chain comprises of approx.1000
amino acids
with a characteristic repeat sequence Gly-X-Y
 X is frequently Proline,Y is often Hydroxyproline
or
hydoxy lysine

10. Collagen I – THE PROTOTYPE

11. Staggered arrangement of collagen

12. FUNCTION OF COLLAGEN
 As a part of extracellular matrix ,maintains tissue architecture
 Supports the epidermis & DEJ with underlying dermis
 Maintains the basement membranes of various organ systems like
respiratory,gastrointestinal,urogenital ,etc.
 Supports the endothelium ,facilitate adhesion of platelets during
vascular injury
 Forms a major part in the architecture of musculoskeletal system
like tendons ,ligaments,cartilage and bones
 Maintains the transparency of lens in eye and supports the stroma
of cornea and vitreous humor

13. BIOSYNTHESIS OF COLLAGEN
Intracellular steps:
 1. Translation of pre-pro chains on the ribosomes
of the rough endoplasmic reticulum
 2. Cleavage of the signal sequence
 3. Hydroxylation of selected prolyl and lysyl
residues
 4. Glycosylation of some hydroxylysyl residues
 5. Formation of intrachain disulfide bonds
 6. Formation of triple helices

14. EXTRACELLULAR MODIFICATIONS
 . Cleavage of peptide extensions by specific
proteases
 Fibril formation
 3. Cross-linking of collagen fibrils by deamination of
hydroxylysine and lysine residues to give aldhehydes,
followed by cross-link formation by reaction of either
(a) 2 aldehydes or (b) 1 aldehydes and
1 -amino group on adjacent molecules

18. APPLIED ASPECTS OF COLLAGEN
 DISORDERS DUE TO DEFICIENT OR
ABNORMAL COLLAGEN SYNTHESIS :
1.synthesis enzymes deficiency 2. mutation of
coding genes
 DISORDERS DUE TO EXCESS COLLAGEN
SYNTHESIS AND ACCUMULATION
 PLACE OF COLLAGEN IN AESTHETICS AND
CLINICAL DERMATOLGY

19. DISORDERS DUE TO
DEFECIENCY OR DEFECTIVE
SYNTHESIS
SCURVY : Due to
def. of Vit.C ,the
hydroxylation step
fails.Vit.C acts as
coenzyme for prolyl
hydroxylase and lysl
hydroxylase

20. MENKES
DISEASE
X linked disorder
associated with
copper deficiency
 Lysyl oxidase
requires copper for
proper function. This
enzyme cross-links
tropocollagen into
strong collagen
fibrils.
Lead to weakened
bones and cartilage

21. OSTEOGENESIS IMPERFECTA
 Also called brittle bone disease, inherited as AD disorder
 due to a lack of type I collagen.
 90% of cases due to mutations in the COL1A1 or COL1A2 genes.
 A least nine different types of OI.
Type I ( most common type ): Collagen is of normal quality but produced in insufficient
quantities. Associated with easy fractures,Slight spinal curvature,Loose joints ,Poor
muscle tone Discoloration of the sclera
Type II (the most lethal) ; Collagen is not of a sufficient quality or quantity.
Severe respiratory problems due to underdeveloped lungs
Severe bone deformity and small stature .Most cases die within the first year of life
due to respiratory failure or intracerebral hemorrhage
Type III ( progressive and deforming) : Enough collagen is made but it is defective.
Bones fracture easily, sometimes even before birth Bone deformity, often severe
Respiratory problems possible Short stature, spinal curvature and sometimes barrel-
shaped rib cage Triangular face ,Loose joints ,discoloration of sclera
Type IV : deforming, but with normal sclerae most of the time

23. ehlers danlos syndrome
13 types of Ehlers-Danlos syndromes, with a
significant overlap in features.
Classical EDS
 extremely elastic , fragile skin and bruises easily
 wide atrophic scars (flat or depressed scars)
 joint hypermobility. and spheroids (fat-containing cysts on forearms
and shins)
Hypermobile EDS
 joint hypermobility affecting both large and small joints
 recurrent joint dislocations and subluxations ,
 soft, smooth and velvety skin with easy bruising
 chronic pain of the muscles and/or bones
Dermatosparaxis EDS
 extremely fragile skin leading to severe bruising and scarring
 saggy, redundant skin, especially on the face
 Brittle Cornea Syndrome (BCS) characterized by thin cornea, early
onset progressive keratoglobus and blue sclera

24. Vascular EDS
 thin, translucent skin ,fragile and bruise easily
 Arteries and certain organs such as intestines tend to
rupture.
 short stature; thin scalp hair; and large eyes thin nose, and
lobeless ears.
 Joint hypermobility confined to the small joints .
 Other common features include club foot; tendon and/or
muscle rupture; acrogeria
Kyphoscoliosis EDS -
 severe hypotonia at birth, progressive scoliosis (present from birth),
 scleral fragility , unusually small corneas; and osteopenia (low
bone density).
 "marfanoid habitus" characterized by long, slender fingers
(arachnodactyly); unusually long limbs; and a sunken chest (pectus
excavatum) or protruding chest (pectus carinatum)

26. Genetic mutation of some specific collagens
 Collagen VII (AD/AR) : DYSTROPHIC EPIDERMOLYSIS BULLOSA
EPIDERMOLYSIS BULLOSA ACQUISITA
BULLOUS SLE
 COLLAGEN XVII (AR) : JUNCTIONAL EPIDERMOLYSIS BULLOSA
 COLLAGEN TYPE IV( BASEMENT MEMBRANE DISORDERS)
alpha3 chain mutation or antibody: GOOD PASTURE SYNDROME
alpha5 chain mutation or antibody : ALPORT SYNDROME

27. DEJ FLASH BACK

28. DISORDERS OF EXCESS SYNTHESIS AND
DEPOSITION OF COLLAGEN
1 . Keloids and hypertrophic scars
 TGF-β signaling pathway
 Presence of α1-globulin inhibits
collagenase
2. Dermatofibroma
3. connective tissue collagenoma
 a/w increased collagen synthesis with
vertical orientation
 multiple papular connective tissue nevus
especially on trunk and upper extremeties
4.SCLERODEMA and other autoimmune
connective tissue disorders

29. PLACE OF COLLAGEN IN AESTHETICS AND COSMETIC
DERMATOLOGY
 The advent of various aesthetics procedures has changed the face of Modern
Dermatology
 Procedures commonly in vogue are augumentation/voluminizing by Fillers ,
dermabrasion, chemical peeling, BOTOX treatment , liposuction ,etc.
 Of note fillers in the form of hyaluronic acid ,PMMA, PLLA and Collagen are
being used to treat fine lines and coarse wrinkles
 Collagen fillers in form of human collagen ,COSMODERM and COSMOPLAST .
 Collagen also used as a gel in wound healing and as a scaffold for bone graft
 Hydolysed collagen is used as a supplement to promote healthy skin and bones.

30. AGEING ?......... WHY?
 THE CAUSE :
1.FAILURE OF INTRINSIC ANTIOXIDATIVE MECHANISM
2. ACCUMULATION OF REACTIVE OXYGEN SPECIES
3. TELOMERE SHORTENING
4. DECREASED SYNTHESIS AND INCREASED DERADATION OF
COLLAGEN
 Visible skin ageing occurs due to collagen degradation because of imbalance
between MMPs/COLLAGENASES and synthesis of collagen
 We can only fantasize to reverse ageing like the reverse ageing of BENJAMIN
BUTTON of the movie “THE CURIOUS CASE OF BENJAMIN BUTTON “
 Human efforts can only delay the Inevitable – senescence onto death

31. DON”T FROWN ,KEEP SMILING