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What is the “HIF” hypoxic response of the Nobel Prize in Medicine?


It is well known that marathons conduct “high altitude training” to increase endurance.
The purpose of this is to increase the number of red blood cells that carry oxygen in the body,
and increase physical endurance by training at high altitudes with less oxygen.
When oxygen is low, the body adapts.
So, by what kind of mechanism does this happen?
This discovery of the mechanism by which cells detect and respond to hypoxia has recently
earned the Nobel Prize in Physiology or Medicine for three researchers in North America.

HIF discovered, HIF explained

We cannot live without oxygen.
Therefore, when oxygen is deficient, a hormone called “erythropoietin” increases, and many red
blood cells are produced.
Up to now, this has been known for some time, but it seems that a more detailed mechanism
has been found in the past 30 years.

First, in the 1990s, Gregg Semenza of Johns Hopkins University in the United States
discovered a protein that activates the erythropoietin gene during hypoxia, and named it
“Hypoxia-inducible factor (HIF)”
And it was two people, Peter Ratcliff of Oxford University in the United Kingdom and William
Kaelin of Harvard University, who clarified the molecular mechanism by which HIF switches the
hypoxia response gene on and off, according to oxygen saturation.
These three were awarded the Nobel Prize in Physiology or Medicine.

New drugs based on HIF

In September of this year, a new drug was developed based on this discovery, and was
approved in Japan.
This medicine is for patients with chronic kidney disease during the dialysis stage.
The kidney not only excretes waste products, but also has the function of secreting hormones
(endocrine function), and erythropoietin is also produced in the kidney. Therefore, when kidney
function declines due to chronic kidney disease, erythropoietin productivity also declines,
resulting in a decrease in the number of red blood cells and anemia.
This is called “renal anemia”.
A drug called “Evrenzo” (generic name: Roxadustat) has recently been approved as a drug to
combat renal anemia associated with chronic kidney disease. This drug activates HIF,
increasing the number of red blood cells and preventing anemia.

Expecting cancer treatment

In addition, HIF has been reported to be associated with chronic inflammation, cancer-related
angiogenesis, and metastasis.
Cancer cells actually have a low ability to ingest oxygen, but they still grow indefinitely because
they use this HIF to form blood vessels.
By the way, Mr. Mikata, who won the Nobel Prize in Physiology or Medicine this time, said that
Mr. Semenza was a pediatrician and a researcher, Mr. Kaelin was originally an oncologist, and
Mr. Ratcliff was a nephrologist.
It is expected that this discovery will lead to the treatment of various diseases due to the fact
that we have come to the research of “HIF” by way of various fields.

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