Home Blog of Signal Transduction GPCR & G Protein PKD Protein kinase D1 promotes the survival of random-pattern skin flaps in rats

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Protein kinase D1 promotes the survival of random-pattern skin flaps in rats

Background: In reconstructive surgery, random skin flaps are commonly used tools to cover skin defects, however, their applicability and size are limited by post-operative complications such as marginal ischemia-reperfusion injury and flap necrosis. Protein kinase D1 (PKD1), a calcium/calmodulin-dependent serine/threonine kinase, is known to induce angiogenesis and has been shown to mitigate ischemia in cardiovascular diseases. However, the role of PKD1 has not been investigated in skin flaps.

Method: Seventy-five male Sprague-Dawley rats with skin flaps were randomly divided into three groups: control, PKD1, and CID755673. Seven days following surgery, we assessed the general view and survival rate of the flap using histological analysis. Laser Doppler and lead oxide/gelatin angiography were used to evaluate microcirculation blood flow. Histopathological changes, neovascularization and microvascular density (MVD). were examined and calculated using microscopy after H&E staining. Protein expression levels were determined using immunoblotting and immunohistochemistry techniques.

Result: PKD1 significantly improved flap survival by upregulating angiogenic factors VEGF and cadherin5 and increasing antioxidant enzymes SOD, eNOS, and HO1, as well as reducing caspase 3, cytochrome c, and Bax expression, and attenuating IL-1β, IL-6, and TNF-α. In the PKD1 group, PKD1 increased neovascularization, and blood flow and flap survival areas were larger as compared to the control and CID755673 groups.

Conclusion: These findings show that PKD1 accelerates angiogenesis, reduces oxidative stress, and impedes apoptosis and inflammation, thus resulting in improved flap survival. Our observations indicated that PKD1 could be a therapeutic target for flap failure treatment.

Comments：

The study investigated the role of protein kinase D1 (PKD1) in skin flaps using male Sprague-Dawley rats. The results showed that PKD1 upregulated angiogenic factors VEGF and cadherin5, increased antioxidant enzymes SOD, eNOS, and HO1, reduced caspase 3, cytochrome c, and Bax expression, and attenuated IL-1β, IL-6, and TNF-α. PKD1 also increased neovascularization and blood flow, resulting in improved flap survival compared to the control and CID755673 groups. The findings suggest that PKD1 could be a therapeutic target for flap failure treatment by accelerating angiogenesis, reducing oxidative stress, and inhibiting apoptosis and inflammation.

Related Products

Cat.No. Product Name Information
S7188 CID755673 CID755673 is a cell-active pan-PKD1/2/3 inhibitor with IC50 of 180 nM, 280nM, and 227 nM, respectively, about 200-fold selectivity over other CAMKs.

Related Targets

PKD CaMK