Abstract

Pancreatitis is a life-threatening disorder for which currently there is no targeted
therapy. Most studies of this disease examine the inflammatory pathways following
injury.A novel, alternate strategy would be to examine the recovery mechanisms of the
pancreas in response to injury.
Based on 2 key observations from the Holy Quran:
1) That regeneration of organs, including the pancreas, can occur,
2) That specific scaffolds mediate this regeneration and 1 key observation in
clinical medicine
(1) that valproic acid (VPA), a drug which is definitely associated with pancreatitis,
is an inhibitor of an important class of epigenetic proteins the histone deacetylases
(HDACs), we hypothesized that HDACs are crucial for activating the programs
necessary for pancreatic recovery. Using sophisticated experimental models of
pancreatic recovery, we determined that (1) HDACs modulate pancreatic recovery
after injury and (2) that there are critical developmental pathways during recovery
that are affected by the HDACs.
It is anticipated that these studies will, God-willing, not only provide an
understanding of a mechanism of drug-induced pancreatitis, namely due to VPA,
but more importantly, the work will open up a new therapeutic paradigm that
exploits Epigenetics to control recovery and regeneration of the pancreas.
The Quran provides a distinct sequence by which an embryo forms, and it also
suggests the possibility of whole organism or specific organ renewal along the lines
of the initial formation. In particular, the Quran mentions an “izama,” or substrate,
that is necessary to allow for the completion of the process of embryogenesis.
Based on the principle that regeneration of organs is possible, but along an
identifiable pathway that requires key “izamas,” we hypothesized that, in the
context of pancreatic regeneration after injury, there were key molecular switches
that turned on, or reprogrammed, the organ towards completion of regeneration.
We examined the role of the epigenetic proteins the histone deacetylases (HDACs)
as a key switch and found that they indeed were necessary for turning on the
processes that allowed the final maturation of the regenerating pancreas. We hope
that this insight from the Holy Quran will be beneficial in providing principles for a
pathway through epigenetic reprogramming to enhance organ regeneration after
injury and will thus treat organ-based disorders.