L-Theanine Down-Regulates the JAK/STAT3 Pathway to Attenuate the Proliferation and Migration of Vascular Smooth Muscle Cells Induced by Angiotensin II

Peiling Ben, Monong Hu, Huizhen Wu, Zhengping Zhang, Yanhong Gao, Lan Luo, Zhimin Yin
2018 Biological and Pharmaceutical Bulletin  
L-Theanine, a green tea amino acid derivative, has cardiovascular qualities. The focus of the current evaluation was to examine the suppression of L-theanine on cultured vascular smooth muscle cell (VSMC) proliferation and migration that is prompted by angiotensin II (Ang II). The VSMCs were treated with noncytotoxic concentrations of L-theanine and then stimulated with Ang II. The CCK-8 and Transwell chamber assays were monitored on the proliferation and migration rate, respectively. We
more » ... ectively. We discovered that L-theanine (50 and 100 µM) significantly halted Ang II-induced VSMC proliferation and migration. This was joined by a decline in the amount of cyclin D1. An additional discovery was that L-theanine lowered the proportion of S-phase cells, whereas the number of G1/G0-phase cells in Ang II-stimulated VSMCs was elevated, based on flow cytometry. Western blotting analyses indicated that L-theanine had no impact on extracellularsignal-regulated kinase 1/2 (ERK1/2) activation prompted by Ang II. Nevertheless, L-theanine significantly lowered Ang II-prompted phosphorylation of Janus kinase 2 (JAK2), c-Src tyrosine kinase, and signal transducer and activators of transcription 3 (STAT3). The outcomes revealed that L-theanine subdued the Ang II-prompted proliferation and migration of VSMC, partly via the obstruction of the JAK/STAT3 pathway instead of via just the ERK pathway. Key words L-theanine; vascular smooth muscle cell; proliferation; signal transducer and activator of transcription 3 (STAT3); Janus kinase 2 (JAK2); angiotensin II Angiotensin II (Ang II), a main result of the renin-angiotensin-aldosterone system (RAAS), acts on vascular smooth muscle cells (VSMCs) and induces microartery contraction. VSMCs were chronic exposed to Ang II resulting in cell proliferation, hypertrophy and aging. 1) Abnormal proliferation of VSMCs makes vascular remodeling a pivotal process in the pathogenesis of hypertension. In addition, it is the structural foundation of the decline of hypertension. 2) Looking for drugs that can both inhibit blood pressure and inhibit proliferation of VSMCs is an important strategy to prevent hypertensive diseases. Ang II connects to Ang II type 1 (AT1) receptors and signals via small guanosine 5′-triphosphate (GTP)-binding proteins, including the Rho family, Ras family and Rac family, which control VSMC gene expression, proliferation, migration, and cytoskeletal reorganization. 3) Ang II prompts the mitogen-activated protein kinase (MAPK) pathway, such as the p42/p44 extracellular signal-related kinases (ERK1/2),
doi:10.1248/bpb.b18-00387 fatcat:3j5rv4vl5zezjo6mhaxf5hck7m