P311 Deficiency Leads to Attenuated Angiogenesis in Cutaneous Wound Healing

Abstract

P311 was identified to markedly promote cutaneous wound healing by our group. Angiogenesis plays a key role in wound healing. In this study, we sought to define the role of P311 in skin wound angiogenesis. It was noted that P311 was expressed in endothelial cells in the dermis of murine and human skin wounds. The expression of P311 was confirmed in cultured murine dermal microvascular endothelial cells (mDMECs). Moreover, it was found that knockout of P311 could attenuate the formation of tubes and motility of mDMECs significantly in vitro. In the subcutaneous Matrigel implant model, the angiogenesis was reduced significantly in P311 knockout mice. In addition, wound healing was delayed in P311 knockout mice compared with that in the wild type. Granulation tissue formation during the defective wound healing showed thinner and blood vessel numbers in wound areas in P311 knockout mice were decreased significantly. A reduction in VEGF and TGFβ1 was also found in P311 KO mice wounds, which implied that P311 may modulate the exprssion of VEGF and TGFβ1 in wound healing. Together, our findings suggest that P311 plays an important role in angiogenesis in wound healing.

Reconstruction and Functional Annotation of P311 Protein–Protein Interaction Network Reveals Its New Functions

“…While in myofibroblasts, it enhanced the activity of Ral A (Shi et al, 2006). Other known functions of P311 like the regulation of blood pressure homeostasis (Badri et al, 2013), the regulation of development of fibrosis (Yao et al, 2015; Cheng et al, 2017), the regulation of wounds (Yao et al, 2017), angiogenesis (Wang et al, 2017) and so on are shown in Supplementary Material 8. P311–TGF-β axis signaling was demonstrated to be important signaling that is related to the processes above.…”

“…Compared to the P311 WT mice, the number of inflammatory cells was much lower in P311 KO mice, while the mRNA level of CD14 and CD16 was also much lower in P311 KO mice (Figure 3). It has been proven that P311 could regulate wound healing by accelerating reepithelization (Yao et al, 2017) or by affecting angiogenesis (Wang et al, 2017). It therefore implies that P311 might also regulate wound healing by affecting the inflammation response during wound healing.…”

“…Moreover, we also verified a role of P311 in coagulation. As we had observed the difference in the formation of scabs between P311 WT and P311 KO mice when we made the mice wound healing model (Wang et al, 2017), the bioinformatic analysis predicted the function of coagulation. These strongly implied a function of P311 in coagulation.…”

“…Furthermore, we demonstrated that P311 played a crucial role in renal fibrosis via TGFβ1/Smad signaling (Yao et al, 2015). Recently we showed that P311 accelerated skin wound re-epithelialization by promoting epidermal stem cell migration through RhoA and Rac1 activation (Yao et al, 2017) and that P311 deficiency leads to attenuated angiogenesis in cutaneous wound healing (Wang et al, 2017). These studies have aroused our tremendous and sustained interest in P311 and we therefore continue to study its biological function.…”

What Is the Impact of Depletion of Immunoregulatory Genes on Wound Healing? A Systematic Review of Preclinical Evidence

“…The studies were conducted in United States of America (25.9%) [ 27 , 35 – 40 ]; Japan (18.5%) [ 26 , 41 – 44 ]; Germany (11.1%) [ 45 – 47 ]; Brazil, Canada, and China (7.4%, each) [ 28 , 29 , 48 – 51 ]; and Australia, Singapore, Netherlands, Spain, Taiwan, and Switzerland (3.7%, each) [ 52 – 57 ]. The approval for the use of animals in experimental procedures by the Animal Use and Care Committee was mentioned in 85.2% of the studies, and the statistical analyses performed were specified in 81.5% of the studies.…”