RGD Reference Report - Inhibiting toll-like receptor 4 signaling ameliorates pulmonary fibrosis during acute lung injury induced by lipopolysaccharide: an experimental study.

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Inhibiting toll-like receptor 4 signaling ameliorates pulmonary fibrosis during acute lung injury induced by lipopolysaccharide: an experimental study.
Authors:	He, Z Zhu, Y Jiang, H
Citation:	He Z, etal., Respir Res. 2009 Dec 18;10:126.
RGD ID:	4144120
Pubmed:	PMID:20017955 (View Abstract at PubMed)
PMCID:	PMC2803172 (View Article at PubMed Central)
DOI:	DOI:10.1186/1465-9921-10-126 (Journal Full-text)
BACKGROUND: Toll-like receptor 4 (TLR4) is essential in lipopolysaccharide (LPS)-induced fibroblast activation and collagen secretion in vitro. However, its effects on the process of lung fibroblast activation and fibrosis initiation during LPS induced acute lung injury (ALI) remain unknown. The goal of the present study was to determine the effect of inhibiting TLR4 on LPS-induced ALI and fibrosis in vivo. METHODS: The ALI model was established by intraperitoneal injection of LPS in mice. TLR4-small hairpin RNA (shRNA) lentivirus was injected intravenously into the mice to inhibit TLR4 expression. mRNA and protein levels were detected by real-time PCR and Western-blot analysis, respectively. The contents of the C-terminal propeptide of type I procollagen (PICP) in bronchoalveolar lavage fluid (BALF) were detected by ELISA, and the degree of fibrosis was detected by van Gieson collagen staining, the hydroxyproline assay, and alpha smooth muscle actin (alpha-SMA) immunohistochemical staining. RESULTS: Overexpression of TLR4, type I procollagen, alpha-SMA, and p-AKT in murine pulmonary tissue after intraperitoneal injection of LPS at 72 hours and 28 days were detected. Moreover, the degree of fibrosis was shown to increase by ELISA analysis of PICP in BALF, van Gieson collagen staining, the hydroxyproline assay, and alpha-SMA immunohistochemical staining. All of these changes were alleviated by intravenous infection with TLR4-shRNA lentivirus. CONCLUSIONS: Inhibiting TLR4 signaling could ameliorate fibrosis at the early stage of ALI induced by LPS.

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Term	Qualifier	Evidence	With	Reference	Notes	Source	Original Reference(s)
pulmonary fibrosis		ISO	Tlr4 (Mus musculus)	4144120; 4144120	associated with acute lung injury	RGD
pulmonary fibrosis		IMP		4144120	associated with acute lung injury	RGD

Objects Annotated

Genes (Rattus norvegicus)

Tlr4 (toll-like receptor 4)

Genes (Mus musculus)

Tlr4 (toll-like receptor 4)

Genes (Homo sapiens)

TLR4 (toll like receptor 4)

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Inhibiting toll-like receptor 4 signaling ameliorates pulmonary fibrosis during acute lung injury induced by lipopolysaccharide: an experimental study.