Blog Posts

0:00 - 2:30 - Intro

- What we are going to cover on this episode.

2:31 - 6:44 - Fibroblast Heterogeneity, they can be tissue-specific

- An emerging theory in the literature coming to a consesnus; Fibroblasts are different based on what tissue their in.

- Fibroblasts have same identity, but they can put on a different suit which changes their function.

- Superhero Analogy

- 3 Classifications of Fibroblasts (1) Progenitor, (2) Steady-State (Quiescent), (3) Acitvated (Myofibroblasts).

- Steady-state is a signature of being in balance; they act as sentinals

- They look for patterns and disruptions in patterns; MAMP, PAMP, DAMP (Damage-Associated Molecular Pattern)

- Crosstalk with other members of the Immune System (Macrophages)

6:45 - 9:17 - Where Fibroblasts are found and the role of Steady-State Fibroblasts

- Placed in areas where there’s lots of exchange, chokepoints, barriars; i.e. lungs, gut, vasculature.

- They are “landscapers”, they will structurally change the cellular environment (ECM, Fascia) t make sure it’s not to far from Homeostasis.

- How they keep an eye on the landscape.

- Summary of Fibroblasts, “They are on Patrol”

9:18 - 14:38 - The role of Activated Fibroblasts (Myofibroblasts)

- Activation = Inflammation

- Fibroblasts are part of the Immune System

- Different Terminology for Activated Fibroblasts

- They can Mount, Recruit and Modulate an Inflammatory respones.

- What Inflammation actually means.

- Inflammation manifests as Pain in Your Fascia.

- What mechanical changes actually happen in the Fascia when You have too much inflammation and Activated Fibroblasts

- Net = Space gets closed off; Fascia’s primary job is too keep Space open.

14:39 - 19:24 - Is Myofibroblast activation bad?

- Batman Analogy

- Myofibroblasts are suppsed to be transient.

- The problem is when Myofibroblasts stay around too long.

- Myofibroblasts have a contractile, ECM-producing phenotype.

- What a contracture is.

- They secrete pro-inflammatory collagen fibers.

- Tension propagates through mechanotransduction; this flips Fibroblasts to Myofibroblasts

- Tight Fascia begets more tight Fascia until You get Adhesion or Fibrosis.

19:25 - 22:43 - Why chronic Myofibroblast Activation is a problem.

- It loops in on itself.

- Study Quote - Activated Fibroblasts drive chronic Activation

- Another study in the Meta-Analysis - Synovial Fibroblasts can retain stromal memory, they are sensitized to become Myofibroblasts right away if there’s only partial remediation

- Myofibroblasts can remain on standby

22:44 - 26:58 - The Gut-Fascia Axis

- Fibroblasts are strategically placed at Your gut lining.

- Fibroblasts have 2 well-studied receptors Pattern Recognition Receptors; TLR4 (Toll-like Receptor 4) and NOD-like Receptors (Nucleotide Oligiomerization Domain).

- Your Gut lining is Your “inside-skin”.

- When LPS moves from Your gut to the serum; it binds to TLR4 and flips Fibroblasts to Myofibroblasts

- Batman Analogy for how NOD-like Receptors work.

- They can respond to cytokines (Biochemical Activation)

26:59 - 30:36 - Why response to cytokines is so critically important.

- 70% of Your Immune population exists under Your gut lining.

- If Gut is compromised all members of the Immune System release Pro-Inflammatory cytokines.

- TNFa is one of many cytokines that activate fibroblasts

- How the gut is directly related to pulmonary fibrosis.

- Activated Fibroblasts will release their own pro-inflammatory cytokines and mechanical tensioning.

- How TNFa from Fibroblasts can drive fibrosis lungs.

30:37 - 34:12 - Other Pro-inflammatory cytokines that activate Fibroblasts