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.