Introduction
Due to its convenience and flexibility, skin flap has become an ideal
material for the repair of all tissue defects in plastic and
reconstructive surgery 1-3. Although the blood
circulation of the random pattern flap is not specific, and distal flap
necrosis is the most common postoperative
complication4. it is mostly utilized to rebuild skin
defects related to congenital disorders, trauma, diabetes, and
cancer-associated abnormalities. If the flap length-to-width ratio
exceeds 2:1, the distal portions become liable to necrosis, thus
limiting its clinical use5. Angiogenesis is a critical
factor in skin flaps survival; hence, adequate angiogenesis is a
guarantee of flap survival following reconstructive
surgery6. Oxidative stress and apoptosis are key
contributors in skin flap necrosis in previous
studies7. Suppressing necrosis of skin flaps requires
lowering oxidative stress, inhibiting apoptosis, and preventing
ischemia-reperfusion (I/R) injury8, 9. To improve
random skin flap survival, medical treatments that reduce oxidative
stress and apoptosis and stimulate angiogenesis might be a suitable
choice.
PKD1, also known as PKC-μ, is a serine/threonine kinase that is a PKD
family member, which is a calcium/calmodulin-dependent kinase (CaMK)
family subgroup10. It can function on various pathways
and is involved in controlling a variety of biological
processes11, 12. PKD1 is a critical regulator of tumor
angiogenesis, promoting the development of new blood vessels
effectively13. PKD1 has been shown in some studies to
protect cardiomyocytes from damage caused by regional myocardial
ischemia and hypoxia14-16. However, the effects of
PKD1 on flaps are unknown.
CID755673 is a PKD1-specific inhibitor that was employed in the current
study. Unlike many other kinase inhibitors, CID755673 has a high degree
of selectivity due to the presence of the kinase ATP binding
domain17. It has been utilized to suppress the growth
and motility of prostate cancer by inhibiting the process of PKD
regulation, including class IIa HDAC phosphorylation18,
19. As a result, we hypothesize that PRKD1 (an exogenous recombinant
PKD1) may reduce oxidative stress, increase angiogenesis, and prevent
cellular apoptosis, leading to the enhancement of random flap survival.