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Protection from lipopolysaccharide-induced pulmonary microvascular endothelial cell injury by activation of hedgehog signaling pathway

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Abstract

Pulmonary microvascular endothelial cells (PMVECs) are critically involved in the pathogenesis of acute lung injury. Hedgehog signaling pathway plays a fundamental role in embryonic development as well as adult morphogenesis and carcinogenesis. As the priming protein of hedgehog signaling pathway, sonic hedgehog (Shh) may recently be advantage for decreasing endothelial injury and promoting the repair of endothelial barrier function. To investigate the expression and role of hedgehog signal pathway in PMVECs injured by lipopolysaccharide (LPS), cells were divided into six groups: control group, LPS group, rhShh group, LPS + rhShh group, rhShh + cyclopamine group, and LPS + rhShh + cyclopamine group. Real time RT-PCR and Western blotting were used to detect the mRNA and protein expression of hedgehog signal molecules including Shh, Patched-1 (Ptc-1) and Gli1 in nucleus. The activity of PMVECs was examined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. In this study, we found that Shh, Ptch1, and Gli1 were expressed in rat PMVECs and their expression decreased when cells were treated by LPS. In the other hand, LPS inhibited the activity of rat PMVECs and caused the cells injury. Activation of Hedgehog signaling pathway by Shh could elevate the activity of PMVECs with pretreatment by LPS. Therefore, hedgehog signaling pathway should play a protective role on injury PMVECs by LPS.

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Acknowledgments

This research was supported by the National Natural Science Foundation of China (30770928 and 30971309), the Key Program of “Eleventh Five-year Plan” for Medical Sci & Tech Research of PLA (06G083 and 08G093).

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Authors and Affiliations

  1. Institute of Respiratory Diseases, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037, China

    Yu Yang, Qi Li, Zhaoxia Deng, Zhiyuan Zhang, Jiancheng Xu, Guisheng Qian & Guansong Wang

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  1. Yu Yang
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  2. Qi Li
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  3. Zhaoxia Deng
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  4. Zhiyuan Zhang
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Correspondence to Guisheng Qian or Guansong Wang.

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Yu Yang and Qi Li equally contributed to this work.

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Yang, Y., Li, Q., Deng, Z. et al. Protection from lipopolysaccharide-induced pulmonary microvascular endothelial cell injury by activation of hedgehog signaling pathway. Mol Biol Rep 38, 3615–3622 (2011). https://doi.org/10.1007/s11033-010-0473-8

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