BCR-Associated Protein 31 Regulates Macrophages Polarization and Wound Healing Function via Early Growth Response 2/C/EBPβ and IL-4Rα/C/EBPβ Pathways

Abstract

The BCR-associated protein 31 (BAP31), a transmembrane protein in the endoplasmic reticulum, participates in the regulation of immune cells, such as microglia and T cells, and has potential functions in macrophages that remain to be unexplored. In this study, we designed and bred macrophage-specific BAP31 knockdown mice to detect the polarization and functions of macrophages. The results revealed that M2 macrophage-associated genes were suppressed in mouse bone marrow–derived macrophages of Lyz2 Cre-BAP31flox/flox mice. Multiple macrophage-associated transcription factors were demonstrated to be able to be regulated by BAP31. Among these factors, C/EBPβ was the most significantly decreased and was regulated by early growth response 2. BAP31 could also affect C/EBPβ via modulating IL-4Rα ubiquitination and proteasome degradation in IL-4–stimulated macrophages. Furthermore, we found that BAP31 affects macrophages functions, including angiogenesis and skin fibrosis, during the wound healing process through IL-4Rα, as confirmed by infection with adeno-associated virus–short hairpin (sh)-IL-4Rα in Lyz2 Cre-BAP31flox/flox mice. Our findings indicate a novel mechanism of BAP31 in regulating macrophages and provide potential solutions for the prevention and treatment of chronic wounds.

Administration of Liposomal-Based Pde3b Gene Therapy Protects Mice Against Collagen-Induced Rheumatoid Arthritis via Modulating Macrophage Polarization

“…C/EBPβ is one of the key transcription factors that are clearly associated with anti-inflammatory macrophage polarization, 32 while cAMP stimulates the activity of PKA, which subsequently phosphorylate CREB to transcribe C/EBPβ expression. 33 Therefore, we investigated whether Pde3b modulate anti-inflammatory macrophage polarization through cAMP-PKA-CREB-C/EBPβ signaling.…”

BAP31 depletion inhibited adipogenesis, repressed lipolysis and promoted lipid droplets abnormal growth via attenuating Perilipin1 proteasomal degradation

“…Two in vitro MEFs cell culture models demonstrated that BAP31-deficiency repressed the expression of adipogenic markers, and prevented the differentiation to adipocytes. When induced to differentiation, growth arrested preadipocytes synchronously reenter the cell cycle and undergo the required process of MCE, followed by the expression of genes aiming to adipocyte phenotype, including Cyclin D1, Cebpβ, cdk2-cyclin E, and so on 36 , 37 . BAP31-deficiency inhibited Cyclin D1 expression and reduced MCE in 3T3-L1 preadipocytes, consequently attenuated the process of adipogenesis.…”

BAP31 Plays an Essential Role in Mouse B Cell Development via Regulation of BCR Signaling

“…66009-1-Ig) was purchased from Proteintech (Chicago, IL, USA). The Ab against BAP31 was raised in our laboratory as previously described [7]. For cell stimulation, anti-mouse IgM and anti-CD40 were purchased from Invitrogen (catalog no.…”

“…It has been observed that BAP31 is predominantly associated with mature B cells expressing the antigen receptor membrane IgD, while its association with membrane IgM is relatively weak [6]. BAP31 has been found to impact various functions of macrophages, such as angiogenesis and skin fibrosis, during the wound-healing process through IL-4Rα [7]. Given its significance in diverse immune cells, it is necessary to further understand the role of BAP31 in the development of B cells.…”