4039 Sonic Hedgehog Signaling: Evidence for Its Protective Role in Endotoxin Induced Acute Lung Injury Mouse Model

Saturday, 17 October 2015
Hall D1 Foyer (Floor 3) (Coex Convention Center)

Xing Chen, MD , Department of Pediatrics, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China

Yuting Jin , Department of Pediatrics, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China

Xiaoming Hou, MD , Department of Pediatrics, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China

Fengqin Liu, MD , Department of Pediatrics, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China

Chunyan Guo, MD , Department of Pediatrics, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China

Yulin Wang, PhD , Department of Pediatrics, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China

Background: To investigate the protective role of the sonic hedgehog (SHH) signaling associated with a lipopolysaccharide (LPS)-induced acute lung injury (ALI) in a mouse model. 

Methods: Male BALB/c mice were randomly divided into three groups, control, LPS, and LPS-C group. ALI was induced by LPS ip injection (5 mg/kg). The sonic hedgehog inhibitor cyclopamine was given to the LPS-C group (50 mg/kg) at 30 min after LPS injection. Lung injury was observed histologically in hematoxylin and eosin (HE) stained tissue sections, semi-quantified by lung tissue injury score, and the lung tissue mass alteration was measured by wet to dry weight ratio (W/D). mRNA levels of TNF-α, SHH, Patched (PTC) and GLI1 in lung tissue were studied with real time quantitative PCR (RT-PCR), while the protein expression of SHH and GLI1 was determined by western blot analysis.

Results: Lung tissue injury score, W/D, and mRNA expression levels of TNF-α were significantly higher in the ALI mice than the normal mice (P<0.05). The mRNA levels of SHH, PTC, and GLI1 in the ALI mice were significantly higher at 12h and 24h after LPS injection, but not at the 6h time point. Protein production of SHH and GLI1 at 6h, 12h, and 24h in the lungs of ALI mice significantly increased, in a time-dependent manner, compared with that in normal mice. Cyclopamine intervention in ALI mice led to a reduction in mRNA levels of SHH, PTC, and GLI1 as well as SHH and GLI1 protein levels; meanwhile, the pathological injury scores of lung tissues, W/D, and mRNA expression levels of TNF-α increased compared to mice receiving LPS only. 

Conclusions: The SHH signaling pathway was activated in response to LPS-induced ALI, and up-regulation of SHH expression could alleviate lung injury and be involved in the repair of injured lung tissue.