Friday, July 25, 2014

Reading the Signals: Something about Your Liver

Sometimes, it’s OK to blame the messenger. I’m not referring to me, of course. I’m referring to Notch, which is a what, not a who. Notch is a cell signaling system, a protein, and it exists in all animals, including you.

Notch plays a key role in embryonic development, and in our adult selves it’s responsible for a bunch of different cell differentiation processes, employing the “psst, pass it down,” mode of message delivery. The first molecule in a signal pathway receives the note and activates another molecule, which activates another, and so on, until the last molecule is activated and the cell function is carried out. 

So, they pass along messages, these molecules that comprise Notch. We need Notch. It is important in some vital cell functions, but sometimes those chatty molecules get a little too loud and, quite frankly, need to shut the hell up, because higher level Notch signaling and abnormal activation can lead to bad things, like cancer, or multiple sclerosis. Or, as a group of Georgia Tech researchers found out, loud-mouthed Notch can make a diseased liver even worse.

They found this out using zebrafish with fibrotic livers – livers with lots of scar tissue, a symptom of chronic liver disease. Fibrosis typically result in cirrhosis, which means a loss of liver function, which usually comes with a grim choice between a liver transplant and certain death. Basically, it’s a perfect storm of terrible things that feeds on itself, because sustained fibrosis is like putting handcuffs on hepatocytes (liver cells), inhibiting their ability to regenerate and therefore make a heroic, therapeutic response. 

At it’s essence, this is a communication problem, based on the study, led by Chong Hyun Shin, a really nice scientist from South Korea who runs a lab at the Parker H. Petit Institute for Bioengineering and Biosience at Tech (See her picture? Doesn’t she look nice? She is. And she’s smart. And if you want your pickled liver to ever see the bright side of life again, you should be nice to her if you ever meet her, because her research could, maybe, lead you down that sunny path).

Anyway, Shin and her team studied (among other things) the effects that different levels of signaling have on the regeneration of these hepatocytes. Specifically, they discovered that lower level Notch signaling promotes cell regeneration (which is good), while high levels suppressed it (bad). And they discovered another signaling system, Wnt, plays a key role in managing Notch’s message. Wnt, basically, is the guy at the sound board turning down the bass to give the song some needed equilibrium. In other words, Wnt’s interaction with Notch modulates the therapeutic, regenerative capacity of liver cells: Wnt signals can suppress Notch signals, so basically, when Wnt is loud enough to suppress Notch, hepatocyte regeneration can happen. Heal thyselves, liver cells, heal thyselves!

The data, says Shin, “suggest an essential interplay between Wnt and Notch signaling during hepatocyte regeneration in the fibrotic liver, providing legitimate therapeutic strategies for chronic liver failure … ” And there’s the hopeful news for you and your abused liver.
Their findings were published recently in the journal Hepatology, so grab a copy from the magazine rack. I think there’s also a feature story on how the interaction of tequila with some Mexican foods makes your liver do a salsa dance, along with recipes, Q&A’s, and advice from some of the most popular and sexy celebrity scientists working in the field. Or something.

Bottom line, I guess, is that Shin’s study offers an opportunity to balance some of the fundamental drawbacks in stem cell therapy, while opening up new avenues of cellular regeneration therapy, endogenously – inside of you, in other words, which, if you think about it, takes us to a whole new frontier in the locally grown movement. But I wouldn’t start shopping for new, organic human livers at the farmer’s market any time soon.

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