Groundbreaking research reveals how the USP37 enzyme acts as a molecular eraser that promotes keloid formation by regulating c-Myc expression in fibroblasts.
We all have scars. A childhood fall, a kitchen mishap, a surgical procedure—they all leave their mark. For most, a scar is a temporary, fading reminder. But for some, the healing process goes haywire, leading to keloids: raised, thick, and often itchy growths that extend far beyond the original wound. They are a common yet frustrating medical mystery. Now, groundbreaking research is pinpointing the exact molecular culprits, and one in particular, an enzyme named USP37, is taking center stage.
Imagine your skin is a construction site after an injury. Normally, cells called fibroblasts arrive, lay down a framework of collagen (the body's scaffolding protein), and then the site is cleaned up, leaving a neat, flat repair. A keloid is what happens when the foreman loses control.
Fibroblasts multiply out of control.
They produce an excessive amount of collagen, far more than is needed.
The construction site never closes. The scar tissue keeps growing, invading healthy skin.
This is where our key player, USP37, enters the story. Inside our cells, proteins are constantly being tagged for disposal with a small marker called ubiquitin. This is a crucial recycling system. When a protein like c-Myc is ubiquitinated, it's sent to the cellular shredder, and its "GO" signal is silenced.
USP37 is a deubiquitinating enzyme. Its job is to remove the ubiquitin tag. In essence, USP37 is an "eraser" that can save proteins from destruction. The new discovery is that in keloid cells, USP37 is overactive. It is constantly erasing the "destroy c-Myc" order, allowing this powerful growth signal to accumulate and run amok, fueling the uncontrolled scar tissue growth.
To prove that USP37 was the key to keloid formation, researchers conducted a series of elegant experiments. Here's a step-by-step breakdown of their crucial investigation.
The researchers used keloid fibroblasts (KF cells) isolated from actual patient keloids and compared them to normal skin fibroblasts (NF cells).
The results were clear and striking. Silencing USP37 set off a powerful chain reaction:
This experiment proved that USP37 isn't just a bystander; it is a direct driver of keloid formation by stabilizing c-Myc. It provided a clear causal link in the chain: High USP37 → High c-Myc → Out-of-control keloid growth.
The following tables and visualizations summarize the core findings from this critical experiment.
This initial observation confirmed the problem. Values are relative to normal fibroblast levels.
| Cell Type | USP37 Level | c-Myc Level |
|---|---|---|
| Normal Fibroblasts (NF) | 1.0 | 1.0 |
| Keloid Fibroblasts (KF) | 3.2 | 2.8 |
Keloid fibroblasts show dramatically elevated levels of both the "eraser" enzyme USP37 and the growth signal protein c-Myc compared to normal skin cells.
This table shows the powerful effect of turning off USP37.
| Measured Outcome | After USP37 Silencing (vs. Control) |
|---|---|
| USP37 Protein | Decreased by ~70% |
| c-Myc Protein | Decreased by ~65% |
| Cell Proliferation | Decreased by ~60% |
| Collagen Production | Decreased by ~55% |
Reducing USP37 levels led to a corresponding drop in c-Myc, which in turn crippled the two main pathological features of keloids: rapid cell growth and excessive collagen production.
This data strengthens the link between the molecular finding and the physical disease.
| Experimental Condition | Observed Keloid Cell Behavior |
|---|---|
| High USP37 / High c-Myc | Aggressive growth and collagen overproduction |
| Low USP37 / Low c-Myc | Growth and collagen production near normal levels |
| Artificially High c-Myc (even with low USP37) | Keloid behavior is partially restored |
The state of c-Myc is a decisive factor. Keeping c-Myc high, even when USP37 is low, can still drive keloid growth, confirming its central role.
Understanding a disease at the molecular level requires a precise set of tools. Here are some of the key reagents that made this discovery possible.
The primary diseased cells studied, isolated from patient keloid tissue. They are the "model system" for the experiment.
A molecular tool used to "silence" or "knock down" a specific gene (like USP37). It's like a targeted off-switch.
Specialized proteins used to detect and measure specific targets (like USP37, c-Myc, or collagen) within a complex cellular mixture.
Chemical tests that measure how quickly cells are dividing. This is crucial for determining if a treatment can slow down keloid cell growth.
Techniques (like Sirius Red staining) to visually quantify and measure the amount of collagen produced by cells.
The discovery of USP37's role is more than just an interesting biological story; it's a beacon of hope for new therapies. Current keloid treatments—like surgery, steroid injections, or laser therapy—are often invasive and have high recurrence rates.
This research points to USP37 as a promising new drug target. If a medication can be developed to safely inhibit the USP37 enzyme, it could, in theory, restore the natural cycle of c-Myc destruction, calming the overactive fibroblasts and preventing keloid growth from the inside out. By understanding the molecular eraser that won't quit, we are one step closer to finally helping the body close the construction site for good.