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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