The effects of qindan-capsule-containing serum on the TGF-β1/ERK signaling pathway, matrix metalloproteinase synthesis and cell function in adventitial fibroblasts

Abstract

(2013) The effects of qindan-capsule-containing serum on the TGF-β1/ERK signaling pathway, matrix metalloproteinase synthesis and cell function in adventitial fibroblasts, Pharmaceutical Biology, 51:6, 712-721, DOI: 10.3109/13880209.2013 Context: Qindan capsule (QC), a compound used in traditional Chinese medicine, has been used as an anti-hypertensive agent in clinical settings for years. Our previous studies have shown that QC can improve the morphological index of the artery, down-regulate the collagen volume fraction in the media and inhibit the transformation of smooth muscle cells. However, the detailed mechanisms underlying its effects require further investigation, which might provide more scientific evidence for the clinical treatment of hypertensive vascular remodeling (VR). Objective: We investigated the effects of QC-containing serum on the TGF-b1/ERK signaling pathway, cell proliferation, migration, the cell cycle, apoptosis and matrix metalloproteinase synthesis (MMPs) in rat aortic adventitial fibroblasts (AFs). Materials and methods: AFs were cultured through tissue explants in vitro. The levels of extracellular signal-regulated kinase 1/2 (ERK1/2), phospho-ERK1/2 (p-ERK1/2), connective tissue growth factor (CTGF), MMP2 and MMP9 expression were measured by western blotting and RT-PCR. The proliferation and migration of AFs were measured by MTT and transwell migration assays. Cell cycle progression and apoptosis in AFs were analyzed by flow cytometry. Results:The proliferation and migration rates of AFs treated with transforming growth factor b1 (TGF-b1) for 24 h were 2.4 AE 0.75 and 2.2 AE 0.06 times higher than those of untreated AFs, and increases in the expression of p-ERK1/2 (3.7 AE 0.15 times), CTGF (3.3 AE 0.24 times), MMP2 (5.7 AE 0.37 times) and MMP9 (5.4 AE 0.46 times) (p50.05) were observed. Treatment with QC-containing serum significantly down-regulated cell proliferation (1.9 AE 0.06 times), migration (1.6 AE 0.05 times) and the expression of p-ERK1/2 (1.3 AE 0.75 times), CTGF (1.8 AE 0.64 times), MMP2 (1.6 AE 0.65 times) and MMP9 (1.4 AE 0.46 times) (p50.05). We also found that QC-containing serum down-regulated the percentage of cells in the G1 phase by 1.6 AE 0.43 times and increased early-phase apoptosis by 2.3 AE 0.33 times (p50.05) in AFs. Conclusions: QC effectively inhibits the proliferation and migration of AFs and changes cell bioactivity and MMPs, possibly through the TGF-b/ERK/CTGF signaling pathway. Our findings may provide new insights into the potential function of QC in preventing or treating hypertension.

Study of the expression and function of ACY1 in patients with colorectal cancer

“…These results all indicate that ACY1 functions via the ERK pathway. Furthermore, activation of ERK increases the expression of TGF-β, another important factor involved in tumor progress (13,(15)(16)(17), and TGF-β could therefore directly attenuate the immune system and promote tumor proliferation (13,17). Thus, decreased expression of TGF-β could lead to tumor inhibition.…”

“…As predicted, this revealed that silencing of ACY1 reduced the level of ERK1 expression in colorectal cancer tissue, which indicates that there is an overexpression of ERK1 along with ACY1 in colorectal cancer. In addition, since it is well known that activation of ERK leads to increased TGF-β1 expression (13,15,16), the association between ACY1 and TGF-β1 expression was measured, which revealed a positive association between the two. The results of the present study indicate that the ERK and TGF-β1 function downstream of ACY1 and facilitate the tumor-promoting effect of ACY1.…”

“…In small cell lung cancer (SCLC), renal cell carcinoma and liver cancer ACY1 expression has been demonstrated to be significantly reduced (10)(11)(12)(13), suggesting that ACY1 serves a role in inhibiting tumorigenesis. Limited studies have investigated the detailed function and mechanism of ACY1 in tumor proliferation, and certain previous studies have reported that activation of ERK 1/2 and expression of TGF-β may be implicated in this process (13)(14)(15)(16). However, the role of ACY1 in gastrointestinal cancer remains unclear.…”

STAT3-mediated MMP-2 expression is required for 15-HETE-induced vascular adventitial fibroblast migration

“…Excessive or inappropriate expression of MMP expression may contribute to the pathogenesis of tissue-destructive processes in a wide variety of diseases, including pulmonary hypertension [11]. Matrix metalloproteinase-2 (MMP-2) is expressed ubiquitously in various cell types including cardiomyocytes, endothelial cells, fibroblasts, and vascular smooth muscle cells and plays a crucial role in angiogenesis regulation [12][13][14]. MMP-2 and -9 are important players in several cardiovascular diseases including atherosclerosis, ischemic heart disease, and heart failure [15][16][17].…”

Safflower Yellow Inhibits Angiotensin II–Induced Adventitial Fibroblast Proliferation and Migration

“…Hypertension is a highly prevalent disorder and a major risk factor for cardiovascular diseases (2). Vascular remodeling (VR) occurs during normal angiogenesis and under various pathological situations, including hypertension (3). VR is an active process of structural alteration that involves changes in at least four cellular processes -cell growth, cell death, cell migration, and the production or degrada tion of the extracellular matrix -and is the common pathological basis of a variety of cardiovascular diseases (4).…”