GSE171372
PDL1 triggered from binding eIF3I contributes to ameliorate diabetes associated wound healing defects by regulating IRS4
We report the application of the transcriptome profiling (RNA-seq) for high-throughput profiling of PD-L1 overexpression in HaCaT cells Overall design: Background: Persistent chronic inflammation and delayed epithelialization lead to stalled healing in diabetic ulcers (DU). PDL1, a widely accepted immune checkpoint molecule, shows activities of anti-inflammatory and proliferative in healing defects. However, the role of PDL1 in DU pathogenesis remain unknown. Methods: Histology and Immunohistochemistry (IHC) staining, Western blot and quantitative real-time polymerase chain reaction (RT-qPCR) were used to examine the expression of eIF3I, PDL1, and IRS4 in DU wounds and HaCaT cell lines. The effects of eIF3I, PDL1, and IRS4 on the proliferation, migration and invasion of HaCaT cells were detected using CCK8, RT-qPCR, wound-healing, and transwell assay. The ability of anti-inflammatory was detected by RT-qPCR. Furthermore, IP-MS, Co-IP, RNA-seq, western blot, and rescue experiments were adopted to explore the regulation relationship among eIF3I, PDL1, and IRS4. Results: Lower level of PDL1 was found in DU tissues, which might contribute to delayed wound closure. Exogenous PDL1 has therapeutic effects in DU healing process via accelerating re-epithelialization and attenuating prolonged inflammation. In vitro assay demonstrated that overexpression of PDL1 could accelerate HaCaT cells proliferation, migration, invasion, and decrease inflammatory response, whereas silencing of PDL1 could suppress those phenotypes. Mechanistically, PDL1 binded with eIF3I and promoted cutaneous diabetic wound healing through down-regulating IRS4. Relevant to the clinic, we found that human diabetic wounds had elevated IRS4 and reductions in eIF3I and PDL1 compared with normal skin. Conclusion: Overall, PDL1 ameliorates diabetes associated wound healing defects by interacting with eIF3I involving regulation IRS4. PDL1 can serve as a potential therapeutic target in DU.