Journal Article
Mathay, C., Pierre, M., Pittelkow, M.,
Depiereux, E., Nikkels, A., Colige, A., et al. (2010). Transcriptional
profiling after lipid raft disruption in keratinocytes identifies critical
mediators of atopic dermatitis pathways. [Journal Article]. The Journal Of
Investigative Dermatology, 131(1), pp. 46-58.
This primary research article goes down to the cellular
level in studying atopic eczema. Here’s a quick introduction of the basic
structure of the skin before we delve into the research.
The skin is made up of three layers: the epidermis, dermis
and subcutaneous tissue.
The area we are interested in today is the topmost layer
called the epidermis. Keratinocytes are the predominant skin cells here. They
undergo differentiation to form different kinds of cells in the epidermal
layer. New skin cells are forming at the bottom layer and move toward the top
while the older cells on top die and rise to the skin’s surface. They then
flake off.
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| Epidermis |
In this study conducted by scientists from various Belgium
universities and USA laboratories, further research into the function of membrane
lipid rafts was conducted, with interesting findings related to atopic
dermatitis.
Methods
Quoting verbatim from the article: “whole-genome
transcriptional profiling in MBCD-treated keratinocytes was performed”. In English,
this means that the scientists messed up the fat in the membranes of this skin
cells, than examined them closely.
They measured transcript levels in
the cells immediately after cholesterol depletion, 1 hour later and 8 hours
later.
What does transcript levels refer
to? Transcription is the process of creating a complementary RNA copy of a
sequence of DNA. Keratinocytes respond to cholesterol depletion by inducing the
transcription of genes that help in making cholesterol.
Cholesterol biosynthesis is a major occurrence after fat is
taken out and scientists use this method of studying keratinocytes because
combined with bioinformatics data analyses, they
can identify and characterize lipid raft-dependent transcriptional targets and
cell signaling pathways. Armed with such information, they proceed to do an association
of functions and diseases with lipid raft-disrupted keratinocytes.
Results
The study documented various cell
responses at different points in time, going into detail with the different
types of genes. The results are pretty complex as over 3, 000 genes were
differentially regulated, with some like metalloproteinases being highly
upregulated and other genes downregulated.
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| Diagram showing Differential regulations at Time periods |
What was most significant for our
interest in eczema is that AD associates the most significantly with the
transcriptional profile observed at R0h, and AD is second at R1h after lipid
raft disruption by MBCD. This means eczema sufferers are found to have
this kind of fat-disrupted cell membrane skin cells occurring at time=0h and
1h. This shows that in skin cells of people with eczema, there may be a problem
in lipid raft organization and signaling.
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Illustration of potential networks showing relevant genes and their possible interactions, either immediately after cholesterol depletion (at 0 hours (R0h (a))
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In the second part of the study
they compared AD skin with normal skin by collecting skin biopsy specimens of
acute lesions and surrounding normal-appearing skin of AD patients (average
age: 39 years), as well as biopsy specimens of healthy volunteers (average age:
43 years) after informed consent. The transcript levels of several major
targets of cholesterol depletion were analyzed.
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| Skin Biopsy. http://www.beliefnet.com/healthandhealing/getcontent.aspx?cid=14861 |
Regarding the results of this part
of the study, the article says that: “In summary, when comparing AD skin with
normal skin, increased expression levels of IVL, TGM1, HB-EGF, IL-8, and PLAUR
are detected simultaneously with a decreased expression of FLG and LOR.”
How clever! We will take their word
for it. These results agree with their results in the first part of the
transcriptional analysis of gene expression in lipid raft-disrupted
keratinocytes, strongly suggesting that membrane organization and signaling
might be disturbed in AD keratinocytes.
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| Normal skin VS Eczematous Skin http://www.yalescientific.org/2011/05/the-mechanisms-and-perception-of-itch/ |
Understanding more about genes
connected to atopic dermatitis may not have a direct impact on the day-to-day
skin care program of eczema sufferers, but it portends future developments in
possibly gene therapy and personalized medicine. Perhaps in the future
scientists may invent a medicine that can enhance
residual enzyme activity in the membrane of keratinocytes that lead to AD.
The current treatment of eczema is concerned
with managing the symptoms and this research offers the tantalizing prospect of
targeting the root of the problem. But we are like people in Plato’s cave who
cannot ‘see’ and our evaluation of the importance of this study can at best be
speculative. Its worth would eventually be revealed with the passing of time
and progress of medicine.
