1. ITIH4 reversed the effects of thrombin on VSMCs stiffness via JNK and ERK signaling pathway.
- Author
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Tian L, Zhao S, Ding F, and Zhang R
- Subjects
- Animals, Myocytes, Smooth Muscle metabolism, Myocytes, Smooth Muscle drug effects, Vascular Stiffness drug effects, Cells, Cultured, Rats, Humans, Rats, Sprague-Dawley, Peptide Hormones metabolism, Peptide Hormones pharmacology, Peptide Hormones genetics, Thrombin pharmacology, Thrombin metabolism, MAP Kinase Signaling System drug effects, Muscle, Smooth, Vascular metabolism, Muscle, Smooth, Vascular cytology, Muscle, Smooth, Vascular drug effects
- Abstract
Vascular smooth muscle cell (VSMCs) is one of the important cell types in artery. VSMCs stiffening may regulate vascular stiffness and contribute to the development of vulnerable plaques. Thrombin, an enzyme in coagulation system, is involved in pathological processes of atherosclerosis. Inter-alpha-trypsin inhibitor heavy chain 4 (ITIH4) plays an important role in regulating inflammation and may have cardiovascular protective effect. Therefore, the elucidation of the mechanisms underlying ITIH4-mediated VSMCs stiffening helps to provide new ideas and potential targets for the diagnosis and treatment of atherosclerosis. In this study, we used specific ITIH4 expression vector and siRNA methods to transfect VSMCs. Our results found that ITIH4 expression increased VSMCs stiffness, meanwhile, ITIH4 siRNA decreased VSMCs stiffness. ITIH4 increased acetylated α-tubulin and inhibited ERK1/2 and JNK, but not P38 MAPK. ERK inhibitor (PD98059) or JNK inhibitor (SP600125) treatment increased acetylated α-tubulin expression and cell stiffness in VSMCs. ITIH4 was downregulated by thrombin treatment, ITIH4 partly reversed the effect of thrombin on acetylated α-tubulin and VSMCs stiffness. These results indicated that ITIH4 regulated acetylated α-tubulin expression in VSMCs and was against the effects of thrombin on VSMCs stiffness. JNK and ERK signaling pathways were proved to participate in this process., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)
- Published
- 2024
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