p38α in macrophages aggravates arterial endothelium injury by releasing IL-6 through phosphorylating megakaryocytic leukemia 1

Abstract

Background Macrophages regulate the inflammatory response and affect re-endothelialization. Inflammation and macrophages play important roles in promoting tissue repair, but p38α mitogen-activated protein kinase's role in re-endothelialization is unknown. Methods and results Wire injuries of carotid arteries and Evans blue staining were performed in macrophage-specific p38α-knockout (p38α fl/fl LysMCre +/- ) mice and control mice (p38α fl/fl ). Re -endothelialization of the carotid arteries at 3, 5 and 7 days was significantly promoted in p38α fl/fl LysMCre +/- mice. In vitro experiments indicated that both the proliferation and migration of endothelial cells were enhanced in conditioned medium from peritoneal macrophages of p38α fl/fl LysMCre +/- mice. Interleukin-6 (IL-6) level was decreased significantly in macrophages of p38α fl/fl LysMCre +/- mice and an IL-6-neutralizing antibody promoted endothelial cell migration in vitro and re-endothelialization in p38α fl/fl mice in vivo . Phosphoproteomics revealed that the phosphorylation level of S544/T545/S549 sites in megakaryocytic leukemia 1 (MKL1) was decreased in p38α fl/fl LysMCre +/- mice. The mutation of either S544/S549 or T545/S549 sites could reduce the expression of IL-6 and the inhibition of MKL1 reduced the expression of IL-6 in vitro and promoted re-endothelialization in vivo . Conclusion p38α in macrophages aggravates injury of arteries by phosphorylating MKL1, and increasing IL-6 expression after vascular injury.

IMP3 promotes re‐endothelialization after arterial injury via increasing stability of VEGF mRNAhv

“…Activation of endothelial migration and proliferation is believed to be related to re‐endothelialization 51,52 . Therefore, we conducted in vitro experiments to determine endothelial cell‐specific functions of IMP3.…”

“…Activation of endothelial migration and proliferation is believed to be related to re‐endothelialization. 51 , 52 Therefore, we conducted in vitro experiments to determine endothelial cell‐specific functions of IMP3. Surprisingly, IMP3 enhances endothelial cell proliferation, migration whilst repressing apoptosis, which was consistent with murine phenotypes.…”

“…(n = 4). # p > 0.05,*p < 0.05, **p < 0.01 and ***p < 0.001 used as a protective agent after stent implantation to promote reendothelialization and attenuate stent restenosis.Activation of endothelial migration and proliferation is believed to be related to re-endothelialization 51,52. Therefore, we conducted in vitro experiments to determine endothelial cell-specific functions of IMP3.…”

MRTF may be the missing link in a multiscale mechanobiology approach toward macrophage dysfunction in space

“…However, we also recommend further study in microtubule disruption that may alter the p38 MAPK pathways. p38 MAPK is known to mediate MRTF-A phosphorylation, the consequence of which was found recently by Zhang M. et al (2021) to be activation of the MRTF-A/p65 complex to promote IL-6 in Mϕ. Furthermore, the consequence of radiation damage on microtubules is rarely studied although may be negligible ( Zaremba and Irwin, 1981 ; Bruni et al, 2020 ).…”

Progress of Research into the Interleukin-1 Family in Cardiovascular Disease

“…A great deal of research has allowed us to conclude that inflammatory responses are involved in human physiological and pathological processes. [9][10][11][12][13] The interleukin-1 family has numerous family members that stimulate inflammationrelated genes and contribute to intestinal diseases, tumors, rheumatoid arthritis, liver and kidney diseases, skin diseases and neurological disorders [14][15][16][17][18][19] and have been shown to affect human metabolism, sleep, appetite and mood. 20 The interleukin-1 family can be broadly divided into two types, pro-inflammatory, IL-1α, IL-1β, IL-18, IL-33, IL-36α, IL-36β and IL-36γ, and the anti-inflammatory, IL-1Ra, IL-36Ra, IL-37 and IL-38.…”