Disordered collagen production by fibroblasts in response to tissue injury contributes to pulmonary fibrosis (PF). Therefore, elimination of collagen deposition has becoming a potential target in PF treatment which despite standard anti-fibrosis regiment still remains challenge. Curcumin and curcumol are regarded as the main active components extraction from the rhizomes of Curcuma zedoaria, which is widely used for inhibition the proliferation of multiple cells. However, the molecular basis for the function of curcumin and curcumol in limiting fibrogenesis still unknown. In this study, we have investigated the effects of curcumin and curcumol in the fibroblast overproliferation model human lung fibroblast (HLF) inducing by TGF-β1. The growth-inhibitory effects of the components wasn’t observed from 8 to 64 μg/ml. Administration of curcumin or curcumol significantly diminished the level of hydroxyproline hydroxyproline and α-smooth muscle actin (α-SMA), also the collagen Ⅰ (Col-Ⅰ) and collagen Ⅲ (Col-Ⅲ) deposition were reduced in the HLF. Furthermore, related to the collagen synthesis proteins including N-terminal pro-peptide for Type Ⅰ collagen (PⅠNP), N-terminal pro-peptide for Type Ⅲ collagen (PⅢNP) and prolyl-hydroxylase (PHD) were degraded gracefully at dose-dependent manner. Autophagy as the scavenger was crippled in TGF-β1-fibroblast overproliferation HLF, conversely the increased autophagosomes have been spotted in cytoplasm under transmission electron microscope which is consistent with up-regulation of Beclin1 and ATG7 after treatment with curcumin or curcumol in this study. Additionally, blocking autophagy by inhibitor chloroquine (CQ) caused collagen deposition, providing further evidence regard to autophagy activation capacity of curcumin and curcumol. Our findings provide a detailed understanding that the function of curcumin and curcumol on decreasing collagen deposition mediating by autophagy mechanism, which may also inspire the further research on PF at different perspectives.

成纤维细胞响应组织损伤而产生的胶原蛋白紊乱有助于肺纤维化（PF）。因此，消除胶原沉积已成为PF治疗的潜在目标，尽管标准的抗纤维化方案仍然存在挑战。姜黄素和姜黄素被认为是从姜黄的根茎中提取的主要活性成分，广泛用于抑制多种细胞的增殖。然而，姜黄素和姜黄素在限制纤维发生中功能的分子基础仍然未知。在这项研究中，我们研究了姜黄素和姜黄素在TGF-β1诱导的成纤维细胞过度增殖模型人肺成纤维细胞（HLF）中的作用。在8至64μg/ ml范围内未观察到该成分的生长抑制作用。姜黄素或姜黄素的使用显着降低了羟脯氨酸，羟脯氨酸和α-平滑肌肌动蛋白（α-SMA）的水平，并且降低了HLF中的Ⅰ型胶原（Col-Ⅰ）和Ⅲ型胶原（Col-Ⅲ）的沉积。此外，与包括Ⅰ型胶原蛋白（PⅠNP）的N端前肽在内的胶原蛋白合成蛋白有关，Ⅲ型胶原蛋白的N端前肽（PⅢNP）和脯氨酰羟化酶（PHD）以剂量依赖的方式温和降解。自噬由于清除剂在TGF-β1-成纤维细胞过度增殖HLF中的作用而削弱，相反，在透射电镜下已在细胞质中发现了增加的自噬体，这与本研究中姜黄素或姜黄素治疗后Beclin1和ATG7的上调一致。此外，抑制剂氯喹（CQ）阻止自噬导致胶原蛋白沉积，为姜黄素和姜黄素的自噬活化能力提供了进一步的证据。我们的发现提供了详细的了解，姜黄素和姜黄素在减少通过自噬机制介导的胶原沉积中的功能，这也可能激发不同角度对PF的进一步研究。