LPS Promotes Vascular Smooth Muscle Cells Proliferation Through the TLR4/Rac1/Akt Signalling Pathway

Abstract

Background/Aims: Lipopolysaccharide (LPS) is a potent activator of vascular smooth muscle cells (VSMCs) proliferation, but the underlying mechanism remains unknown. In this study, we knocked down Toll-like receptor 4 (TLR4) and Ras-related C3 botulinum toxin substrate 1 (Rac1) expression using small interfering RNA (siRNA) in order to investigate the effects and possible mechanisms of LPS-induced VSMCs proliferation. Methods: VSMCs proliferation was monitored by 5-ethynyl-2’-deoxyuridine staining, and Rac1 activity was measured via Glutathione S-transferase pull-down assay. mRNAs encoding proliferating cell nuclear antigen (PCNA), smooth muscle 22α (SM22α), myosin heavy chain (MYH) and transient receptor potential channel 1 (TRPC1) were detected by qRT-PCR. The expression of total Akt, p-Akt (308), p-Akt (473), SM22α, MYH and TRPC1 protein was analysed by Western blot. Results: Treatment with TLR4 siRNA (siTLR4) or Rac1 siRNA (siRac1) significantly decreased LPS-induced VSMCs proliferation. Moreover, LPS-induced activation of Rac1 through TLR4 was observed. Western blot analysis revealed that transfection with siTLR4 or siRac1 inhibited LPS-induced Akt phosphorylation. We discovered that LPS stimulated VSMCs proliferation via phenotypic modulation and that this effect was partially inhibited by pre-treatment with siTLR4 or siRac1. Further, TLR4 and Rac1 are involved in LPS-induced activation of TRPC1. Conclusion: This study suggests that LPS exerts an effect on VSMCs proliferation and that the TLR4/Rac1/Akt signalling pathway mediates this effect.

Coculture with bone marrow‑derived mesenchymal stem cells attenuates inflammation and apoptosis in lipopolysaccharide‑stimulated alveolar epithelial cells via enhanced secretion of keratinocyte growth factor and angiopoietin‑1 modulating the Toll‑like receptor‑4 signal pathway

“…Additional investigation is required to reveal the detailed association between TLR4 signals and apoptosis in LPS-stimulated AECs. Notably, the data from the present study demonstrated that high doses of LPS induced A549 cell apoptosis, whereas low doses promoted A549 cell proliferation, which is in concordance with previous studies (23,24). Low doses of LPS promote cell proliferation by activating multiple signaling pathways including the phosphatidylinositol 3-kinase/protein kinase B pathway (24).…”

“…Notably, the data from the present study demonstrated that high doses of LPS induced A549 cell apoptosis, whereas low doses promoted A549 cell proliferation, which is in concordance with previous studies (23,24). Low doses of LPS promote cell proliferation by activating multiple signaling pathways including the phosphatidylinositol 3-kinase/protein kinase B pathway (24). Different doses of LPS may have distinct modulatory effects on various cell types (25).…”

The Intersection of Serine Metabolism and Cellular Dysfunction in Retinal Degeneration

“…This may lead to increased synthesis of serine since it is produced from the PHGDH shunt. The increase in serine glycolytic synthesis is linked to the amplified activation of toll-like receptor 4 (TLR-4) after activation by lipopolysaccharide (LPS) [69] or hydrogen peroxide [75]. TLR-4 then induces a cytokine response, namely interleukin-1β [69].…”

Inhibition of proliferation and migration and induction of apoptosis in glioma cells by silencing TLR4 expression levels via RNA interference

“…Although TLRs mediate innate immunity, they are not unique to the innate immune system: In addition to immune cells [monocytes/macrophages, T/B lymphocytes and dendritic cells (29)], they are also expressed in certain non-immune cells, such as endothelial (30), smooth muscle (31) and tumor cells (32). TLR expression levels in tumor cells are key for tumorigenesis and progression, and this is an important topic in tumor research (33).…”