extracellular matrix

Evidence of a phenotypic shift.

One of the most striking findings was the increased expression of genes involved in extracellular matrix, ECM, remodeling and collagen production.

Tumor-associated MECs showed elevated levels of multiple collagen genes, matrix metalloproteinases, MMP2, MMP9, MMP11, and MMP14, and ECM-associated proteins such as SPARC and lumican.

At the same time, these cells demonstrated reduced expression of traditional epithelial markers, including KRT5, KRT7, and KRT14.

This combination of changes suggests a transition away from their normal barrier-forming role and toward a more mesenchymal fibroblast-like phenotype that may contribute to tumor progression.

Got it.

What do you make of the recent CML-ACE paper, uh, which showed that you can engineer an enzyme that basically removed the CML from the extracellular matrix, um, uh, in aged human, uh, tissue samples? So, um, just curious what your, what your thoughts are.

Yeah, of course, I'm absolutely ecstatic about it.

It's a really big step forward towards restoring elasticity of the extracellular matrix.

This enzyme on its own, even if it could be expressed appropriately in vivo, would not do that because CML, the thing that it attacks and removes, is not a cross-link.

It's a, an adduct on just one protein.

Um, the focus that I've had historically is on glycation, non-enzymatic glycosylation, the formation of, uh, new chemical bonds between proteins that are not supposed to be linked together.

Um, but there are various others.

As a result, no two fascia systems are alike.

This collagen and fluid-based matrix of extracellular matrix, ECM, remodels itself along the lines of load, impact, pressure, and stress, aka Davis's Law, making fascia a highly trainable and adaptable system.

And the last bullet point, studies indicate that fascia tissue has six to eight times more sensory nerve endings than red muscle, making it the body's largest sensory organ.

So again, what Bill is saying here, and he, again, super intelligent guy.

And when I get into a strength training, a lot of the exercises I saw athletes doing in the weight room did not look like what I was seeing them do on the court.

And I remembered what I learned from Dr. Gary Gray at the Gray Institute about how we can load any exercise three-dimensionally.

This led me to work with my team to develop a three-dimensional matrix training program that targets the core movement patterns of basketball.

Wright's eight movements are squat, lunge, leap, pivot, jump, hop, reach, swing.

like the fascia tissue sticking to itself, but they're not talking about that.

They're talking about things like adhesion of the cell to the ECM or think about a sperm and an egg interaction they need to adhese together.

Excuse

me

And I did find a couple other articles about integrins, but that was primarily what they were about was how they were looking at different drugs that might target integrins in order to help solve specific pathologies.

So I don't have the biochemistry background to understand those articles.

So I am not even going to attempt to tell you what was happening in them other than they're looking at drugs and And I think we know there's other ways to keep the fascial system healthy and contribute to good communication between the integrins and the cell or the ECM and the cell via the integrins, I should say.

Not that I'm saying we shouldn't be looking at drugs to help people with things.

So go back to thinking about the caveolae and the podosomes because a lot of activity in the vasculature is occurring at those specific membrane loci.

particularly cell intrusion and then cell invasion, for example, a metastatic cancer, or for example, just a macrophage, which involves, remember the extracellular matrix.

So cells have to move through the ECM to get to the tissue boundary to ultimately end up going through endothelial barriers.

So that occurs often enough that we know very well there are pathophysiological as well as normal physiological, like macrophages and neutrophils moving through that way, coming from, again, normal processes and the regulation of the immune response.

But Also, corruption of the regulation of that cellular intrusion invasion when you, of course, look at cancer metastasis, and that could be linked often to obesogenic state and, yes, of course, chronological disease we call aging, primarily discussing chronological aging associated with senescence.

It's non-toxic.

And we can actually target either the upper layers of the skin or deeper in the ECM.

which is then we can sort of like remodel and structure collagen from within and that without any signs of redness, bleeding, any bruising, much safer, more pleasant for the clients.

That's wonderful.

damage? In my signature treatments, I'll use radiofrequency.

which will remodel the tissue.

So it sends off a heat protein response that will help to trigger and remodel collagen production that's in your ECMO.

And also then we will use EMS, which is your electrical muscle stimulation.

The first inflammatory event is what causes inflammation.

neutrophils come in they release peroxide they kind of kill everything and then you have your macrophages come in they kind of eat everything and then you have these fibroblasts that can come in and that's a it's a simplification but the fibroblasts come in and they build back that ECM they're the fibroblasts are kind of the They make the elastin, they make the collagen that you can rebuild your ECM, your extracellular matrix.

So that's kind of how TSC works.

It really reduces that inflammation, allows that wound healing to really kick in.

Well, we have to talk about the mechanical and biochemical characteristics of what first is encountered, and that's the extracellular matrices.

And so we have to start thinking about biochemical and physical signaling that is perceived by cells through the biochemical matrix we call the ECM, the extracellular matrix.

And of course, because it's an extracellular matrix, we have to talk about bidirectional interactions.

That means from the cell out and outside the cell in, of course, in a cell population.

So that means there has to be straight up chemical sensing, such as binding to receptors.

But there's also going to be a mechanosensing.

We know this because the extracellular matrix and the outer leaflet of the plasma membrane are involved in a restructuring of that interaction when we see a change that can then develop into a disease state like a cancer.

So I've talked a lot about adhesions and integrin molecules.