| 20193347 |
Hu JM, Zhong NS: [A preliminary study on the mechanisms of N-acetylcysteine in the inhibition of proliferation and collagen synthesis of human pulmonary fibroblasts.]. Zhonghua Jie He He Hu Xi Za Zhi. 2009 Dec;32(12):897-901.
OBJECTIVE: To study the mechanisms of N-acetylcysteine (NAC) in the inhibition of proliferation and collagen synthesis of human pulmonary fibroblasts. METHODS: The human pulmonary fibroblasts (HFB) were primarily cultured in complete medium of DMEM/F12, with the cell line A549 derived from alveolar epithelia as the control. Different concentrations of NAC were administrated, with or without stimulation by TGF-beta (1) for 24 h. The cell proliferations were tested by methylthiazolyltetrazolium (MTT) and cell cycle detected with flow cytometer. The mRNA expression of type I procollagen was tested with RT-PCR. Proteins of cyclin E, alpha-SMA and STAT-3 were detected with Western blotting. RESULTS: The proliferation of HFB was inhibited significantly by NAC at different concentrations (5, 10, 20 and 40 mmol/L). NAC had no effects on proliferation of A549 at a dose of 20 mmol/L. The cell proportion in G (0)/G (1) phase was increased by NAC at different concentrations (10, 20 and 40 mmol/L), while the changes in S-phase ratio were decreased significantly. Procollagen type Isynthesis was increased by TGF-beta (1) significantly. NAC showed inhibition on procollagen type I synthesis before or after stimulation with TGF-beta (1). Expression of protein cyclin E and alpha-SMA was significantly induced by TGF-beta (1), the relative indensity being 0.98 +/- 0.09 and 1.56 +/- 0.23 respectively. Induction of cyclin E by TGF-beta (1) was attenuated significantly by NAC 20 mmol/L (0.52 +/- 0.04). But alpha-SMA was not changed by NAC 20 mmol/L (1.63 +/- 0.20). Stimulation with TGF-beta (1) and NAC had no effects on expression of STAT-3. CONCLUSIONS: Inhibition on proliferation of HFB by NAC may be through the attenuation of cyclin E. Differentiation of fibroblasts into myofibroblasts was inhibited by NAC through inhibition on alpha-SMA. NAC directly inhibited collagen synthesis. |
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