Aberrant expression of TRIM44, transcriptionally regulated by KLF9, contributes to the process of diabetic retinopathy.

BACKGROUND

Diabetic retinopathy (DR) is the common cause of diabetic vascular complications and it causes blindness. Until now, there are still some patients with DR who lack effective treatment. Tripartite motif containing 44 (TRIM44) has been shown to play a significant role in endothelial cells. However, the role of TRIM44 in DR remains unknown.

METHODS

Diabetes was induced in rats through the administration of an intraperitoneal injection of 65 mg/kg of streptozotocin (STZ). Rat retinal microvascular endothelial cells (RMECs) were subjected to stimulation under high glucose (HG) conditions. A thorough proteomic investigation and bioinformatic analysis were performed to identify the differentially expressed proteins (DEPs) in rat RMECs after blocking TRIM44. A dual luciferase reporter assay was employed to assess the luciferase activity of TRIM44.

RESULTS

TRIM44 was highly expressed in the retinal tissues of rats with diabetes and HG-induced RMECs. In vivo assays suggested that TRIM44 silencing improved the pathological alterations of DR rats as demonstrated by the downregulated expression of isolectin-B4 and VEGFA, along with a decrease in acellular capillaries within the retinal tissues. Knockdown of TRIM44 markedly reduced cell viability, proliferation, migration, invasion, and angiogenesis in HG-evoked RMECs. Mechanistically, TRIM44 was demonstrated to be activated transcriptionally by KLF transcription factor 9 (KLF9), a known facilitator of angiogenesis in DR. In HG-induced cells, the loss of TRIM44 resulted in the reverse of the endothelial cell function caused by KLF9 overexpression. After the comprehensive analysis, 64 upregulated and 38 downregulated DEPs were screened out for a series of functional enrichment analyses.

CONCLUSIONS

Collectively, this study demonstrates that TRIM44 knockdown suppressed diabetes-induced retinal vascular dysfunction in DR.