PEDF is an antifibrosis factor that inhibits the activation of fibroblasts in a bleomycin-induced pulmonary fibrosis rat model

Qin, Xichun; Jia, Caili; Liang, Jingtian; Chen, Jiali; Liu, Xiucheng; Chao, Zhixiang; Qin, Hao; Yuan, Yunsheng; Liu, Zhiwei; Zhang, Zhongming; Dong, Hongyan; Zhang, Hao

doi:10.1186/s12931-022-02027-4

Cited by 10 publications

(8 citation statements)

References 45 publications

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“…Interestingly, in lung tissue of patients with IPF, more PEDF expression was found than in lung tissue of controls 22 . PEDF is suggested to have a protective effect in the pathogenesis of fibrosis 23 and therefore the higher levels found in fibrosis suggest a compensatory mechanism trying to control fibrosis development. Indeed, two studies have shown that increased expression PEDF in macrophages attenuated collagen synthesis by fibroblasts in a macrophage-mediated manner 24,25 .…”

Section: Discussionmentioning

confidence: 99%

Collagen type I alters the proteomic signature of macrophages in a collagen morphology-dependent manner

Vasse

Russo

Barcaru

et al. 2023

Sci Rep

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Idiopathic pulmonary fibrosis is a progressive lung disease that causes scarring and loss of lung function. Macrophages play a key role in fibrosis, but their responses to altered morphological and mechanical properties of the extracellular matrix in fibrosis is relatively unexplored. Our previous work showed functional changes in murine fetal liver-derived alveolar macrophages on fibrous or globular collagen morphologies. In this study, we applied differential proteomics to further investigate molecular mechanisms underlying the observed functional changes. Macrophages cultured on uncoated, fibrous, or globular collagen-coated plastic were analyzed by liquid chromatography-mass spectrometry. The presence of collagen affected expression of 77 proteins, while 142 were differentially expressed between macrophages grown on fibrous or globular collagen. Biological process and pathway enrichment analysis revealed that culturing on any type of collagen induced higher expression of enzymes involved in glycolysis. However, this did not lead to a higher rate of glycolysis, probably because of a concomitant decrease in activity of these enzymes. Our data suggest that macrophages sense collagen morphologies and can respond with changes in expression and activity of metabolism-related proteins. These findings suggest intimate interactions between macrophages and their surroundings that may be important in repair or fibrosis of lung tissue.

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Section: Discussionmentioning

confidence: 99%

Collagen type I alters the proteomic signature of macrophages in a collagen morphology-dependent manner

Vasse

Russo

Barcaru

et al. 2023

Sci Rep

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“…BLM intratracheal administration is the most widely employed experimental model of PF research at present [ 31 ]. Delivering BLM to the lung will lead to lung damage, inflammation response, and subsequent fibrosis [ 32 ].…”

Section: Discussionmentioning

confidence: 99%

Jinlian Xiaodu Decoction Protects against Bleomycin-Induced Pulmonary Fibrosis in Rats

Tao

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Background. Jinlian Xiaodu Decoction (JXD) was reported to have anti-inflammatory and lung protection effects. This study aimed to explore the role and mechanism of JXD on bleomycin (BLM)-induced pulmonary fibrosis (PF). Methods. The UHPLC-Q/TOF-MS system was applied to analyze JXD composition. The PF model was established by BLM intratracheal administration in Wistar rats. Subsequently, BLM-treated rats were intragastrically administered with dexamethasone (DXM, 1 g/kg/d) or JXD (3.5, 7 or 14 g/kg/d). Next, the lung coefficient was calculated; H&E, Masson, and TUNEL staining were used for lung morphological analysis and apoptosis assessment. Bronchoalveolar lavage fluid (BALF) biochemical analysis was conducted to count the inflammatory cell number. The expression of inflammatory factors mRNA in the lung tissue and BALF were measured by qRT-PCR. The content and activity of oxidative stress-related proteins were detected. The expression of PF-related, apoptosis-related, and TGF-β1 pathway-related protein were assessed by immunohistochemistry or Western blot. Results. Twenty-six compounds were identified from JXD in both negative and positive ion modes. In BLM-induced rats, JXD reduced the lung coefficient and alleviated PF injury. JXD decreased inflammatory cell count and TNF-α, IL-1β, IL-6, and MCP-1 content. Meanwhile, JXD blunted BLM-induced oxidative stress and a high level of HYP. Furthermore, TUNEL analysis found that JXD inhibited cell apoptosis and increased Bcl-2/Bax ratio in BLM-induced lung. Moreover, JXD relieved the role of BLM on α-SMA, TGF-β1, collagen I, fibronectin, E-cadherin protein expression, and the phosphorylation of Smad2/3 in PF rat. Conclusion. This study revealed the protective effect and possible element of JXD on BLM-caused PF.

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“…ab178860) antibodies and PPAR-γ inhibitor (GW9662, Catalog No. ab141125): Abcam (Cambridge, MA, USA) [ 16 ]. Anti-rabbit RIP3 (Catalog No.…”

Section: Methodsmentioning

confidence: 99%

PEDF inhibits LPS-induced acute lung injury in rats and promotes lung epithelial cell survival by upregulating PPAR-γ

Xu,

Chen,

Feng

et al. 2023

BMC Pulm Med

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Background The progression of acute lung injury (ALI) involves numerous pathological factors and complex mechanisms, and cause the destruction of epithelial and endothelial barriers. Pigment epithelium-derived factor (PEDF) is an angiogenesis inhibitor and a potential anti-inflammatory factor. The purpose of this study was to investigate the effect of PEDF on lipopolysaccharide (LPS)-induced ALI in rats. Methods In vivo, pathological and injury related factors examination were performed on rat lung to investigate the effect of PEDF on ALI. In vitro, the effect of PEDF on inflammatory injury and apoptosis of lung epithelial type II RLE-6TN cell was evaluated, and the expression of inflammatory factors and related pathway proteins and PPAR-γ (in the presence or absence of PPAR-γ inhibitors) were analyzed. Results In vivo results showed that PEDF inhibited the inflammatory factor expression (TNF-α, IL-6 and IL-1β) and progression of ALI and reduced lung cell apoptosis in rats. In vitro results showed that PEDF could effectively inhibit LPS-stimulated inflammatory damage and apoptosis of RLE-6TN cells. PEDF inhibited the RLE-6TN cell injury by enhancing the expression of PPAR-γ. Conclusions PEDF is an anti-inflammatory factor, which can inhibit apoptosis of lung epithelial cells by upregulating the expression of PPAR-γ and reducing LPS-induced ALI in rats.

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PEDF is an antifibrosis factor that inhibits the activation of fibroblasts in a bleomycin-induced pulmonary fibrosis rat model

Cited by 10 publications

References 45 publications

Collagen type I alters the proteomic signature of macrophages in a collagen morphology-dependent manner

Collagen type I alters the proteomic signature of macrophages in a collagen morphology-dependent manner

Jinlian Xiaodu Decoction Protects against Bleomycin-Induced Pulmonary Fibrosis in Rats

PEDF inhibits LPS-induced acute lung injury in rats and promotes lung epithelial cell survival by upregulating PPAR-γ

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