Regeneration

2 requirements for regeneration after inflammation

intact basement membrane

regenerative capacity

2 possible reasons for repair by fibrosis

basement membrane damaged

no regenerative capacity

lesion only will heal by resolution if ...

wound left alone

regeneration occurs in healing when

significant damage requiring cell proliferation

BUT basement membrane intact

fibrosis usually involves which 3 things

angiogenesis

fibrosis

remodeling

what components must interact during wound healing

regenerating cells

basement membrane

interstitial matrix

growth factors come from which macrophages

M2 (alternatively activated)

main cytokine activating collagen synthesis by fibroblast

IL-13

macrophage effect on matrix metalloproteases

decreases activity

2 mechanism of action of GFs

bind receptor -> healing factor expression

GF and cell interact with ECM

mechanisms of GF function result in what

protein synthesis

proliferation

differentiation

migration

3 types of GFs

autocrine

paracrine

endocrine

3 major categories of GF receptors

RTK -> fast signal

no RTK -> rely on cytoplasmic enzymes

GPCR

what is the difference in function between what macrophage-derived cytokines and macrophage-derived GFs do in healing

cytokines = collagen synthesis

GFs = fibroblast proliferation

how is ECM connected to cells

integrins and cytoskeleton

type I collagen location

skin, bone, tendon

type II collagen location

cartilage

type III collagen location

skin, muscle

type IV collagen location

basement membrane

main cofactors required for collagen synthesis

copper and vitamin C

what enzyme crosslinks extracellular collagen

lysyl hydroxylase

what links collagen to integrins

fibronectin and laminin

what links integrins to cytoskeleton

focal adhesion complexes

initiator of angiogenesis

HIF-a

what occurs when HIF is in an anoxic environment

HIF-a and HIF-b dimer

bind to hypoxia response element on DNA

sequence of angiogenesis

digestion = proteolysis of BM/ECM of parent vessel

migration = endothelial cells toward digested point

proliferation = outward expansion from parent vessel

maturation = forming lumen

cell-cell adhesion = gap junctions and establishment of WBC adhesion molecules

perivascular cell migration = pericytes + smooth muscle

VEGF function

angioblast production

endothelial cell proliferation (R2)

tube formation (R1)

angiopoietin function

bind Tie receptor

Tie1 = stabilize and mature vessel

Tie2 = stop angiogenesis

stop signal for angiogenesis

Tie2 receptor

sequence of events in fibrosis

fibroblast migration toward GF site

fibroblast proliferation

fibroblast synthesize ECM

remodeling

how does intermittent MMP activity cause remodeling

resemble normal collagen structure

TGFb source and function

platelet and M2

macrophage chemotaxis, fibroblast migration/proliferation, synthesis of ECM

conditions for wound healing by primary intention

clean edges

minimal tissue loss

no infection

approximated edges

t/f primary intention wounds have a scar

maybe

second intention wound healing conditions

ragged edges

infection

gaping wound

what is a scab

necrotic slough

common causes of impaired wound healing

infection

location over bony prominence

FB

poor blood flow

malnourishment

steroids

uncommon causes of impaired wound healing

diabetes

osteogenesis imperfecta (collagen I)

Ehlers-Danlos

scurvy

most common species for exuberant granulation tissue

horse (over bony prominence)