A Preliminary Study of the Effect of Semaphorin 3A and Acitretin on the Proliferation, Migration, and Apoptosis of HaCaT Cells

Abstract

Background: Vascular endothelial growth factor (VEGF) is significantly elevated in psoriatic patients and is associated with the severity of the psoriasis. Due to the effect of inhibiting production of VEGF, acitretin can effectively treat psoriasis. Semaphorin 3A (Sema3A) restrain tumor growth and angiogenesis by partially reversing VEGF effects on tumor. However, the role of Sema3A in the pathogenesis of psoriasis is unclear. Aims and Objectives: This study aimed to investigate the effect of VEGF, Sema3A, and acitretin on HaCaT cells, to see whether Sema3A could be a beneficial factor in psoriasis, as well as acitretin. Materials and Methods: Functional analysis of VEGF, Sema3A, and acitretin was carried out using HaCaT cells cultured under different treatments. Cell counting kit-8 method, colony formation assay, flow cytometry, transwell migration, reverse transcription-polymerase chain reaction, and Western blot test were performed to measure proliferation, colony formation, migration, apoptosis, and the expression of Bcl2, Bax, Caspase 3, and Caspase 9 of HaCaT cells. Results: Sema3A and acitretin inhibited the proliferation, colony formation, and migration of HaCaT cells, while induced the apoptosis of HaCaT cells by inhibiting the expression of Bcl2, and promoting the expression of Bax, Caspase 3, and Caspase 9, which were opposite to VEGF. Sema3A and acitretin partially reversed the function of VEGF. Conclusions: Like acitretin, exogenous supplement of Sema3A may correct the abnormal proliferation and apoptosis procedure of HaCaT cells, and partially reverse the function of VEGF.

Identification of biomarkers related to angiogenesis in myocardial ischemia-reperfusion injury and prediction of potential drugs

“…Further analysis using CMap revealed that acitretin, derived from etretinate through a structural transformation from an ester to an acid structure, promotes normal keratinization by inhibiting abnormal proliferation and differentiation of keratinocytes. Additionally, avasimibe has the ability to regulate VEGF and participate in microvascular formation, thereby exerting its therapeutic effects [ 44 ]. Bortezomib, a novel proteasome inhibitor, has been shown to possess anti-inflammatory effects by inhibiting the activation of NF-κB, effectively alleviating angiotensin II-induced hypertension and aortic remodeling [ 45 , 46 ].…”

The Involvement of Semaphorins in the Pathogenesis of Skin Diseases

“…Sema3A competes with VEGF for binding to the NRP1/NRP2 coreceptors to inhibit the mitogenic effects of VEGF in endothelial cells, leading to apoptosis and inhibition of migration in breast cancer cell lines [15]. In hematopoietic and leukemic cells, Sema3A can also partially reverse the effects caused by VEGF [16]. The action of semaphorins is shown in Figure 1.…”