Expression and Significance of Krüppel-like Factor 4 in Experimental Pulmonary Fibrosis_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

CHEN Xuefen ^1# , JI Wenjie ^1# , HU Daochuan ¹ , MA Yongqiang ¹ , ZHOU Xin ² , WEI Luqing. ¹

Department of Respiratory and Critical Care Medicine, The Affiliated Hospital of Logistics University of Chinese People’s Armed Police Forces. Tianjin, 300162, ChinaCorresponding Author: WEI Lu-qing, E-mail: luqing-wei@ 163. com;

Corresponding author：

Keywords：

Krüppel-like factor 4; Pulmonary fibrosis; Bleomycin; Mice

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Objective To investigate the expression and significance of Krüppel-like factor 4 ( KLF4) in the lung tissues of mice with bleomycin-induced pulmonary fibrosis.
Methods C57BL/6 mice were randomly divided into a control group and a BLM group. The mice in the BLM group were given a single intratracheal injection of bleomycin ( 2.5 mg/kg) , while those in the control group were injected with isodose physiological saline. The mice were sacrificed at the 12h and on the day 1, 2, 3, 7, 14 and 28, then HE stain and Masson’s trichrome stain were used to detect the architecture of alveolar and the deposition of cellularity and collagen. Real time-polymerase chain reaction ( RT-PCR ) and immunohistochemical technology were performed to investigate the expression of KLF4.
Results In the bleomycin-induced pulmonary fibrosis, acute inflammation was observed on the day 1, 2 and 3, the inflammation was exacerbated and the collagen deposition began to be observed on the day 7, the architecture of alveolar was destroyed and the collagen deposition was more obvious on the day 14, while the alveolar structure was nearly recovered to normal, and the inflammation and collagen deposition were attenuated on the day 28. The expression of KLF4 mRNA increased from the day 1, then decreased, arrived at the minimumon the day 3, and then gradually increased until the day 28. The trend of KLF4 protein expression showed roughly the same as the KLF4 mRNA level, which started to increase on the day 1, then decreased, arrived at the minimum on the day 3,then gradually increased until the day 14 and then decreased again.
Conclusion The expressions of KLF4 mRNA and protein are dynamically changed in the process of experimental pulmonary fibrosis, suggesting KLF4 may contribute to the pathogenesis of pulmonary fibrosis.

Citation： CHEN Xuefen,JI Wenjie,HU Daochuan,MA Yongqiang,ZHOU Xin,WEI Luqing.. Expression and Significance of Krüppel-like Factor 4 in Experimental Pulmonary Fibrosis. Chinese Journal of Respiratory and Critical Care Medicine, 2013, 12(5): 509-512. doi: Copy

1.	McConnell BB, Yang VW. Mammalian Kruppel-like factors in health and diseases. Physiol Rev, 2010, 90: 1337-1381.
2.	Zhou Y, Hofstetter WL, He Y, et al. KLF4 inhibition of lung cancer cell invasion by suppression of SPARC expression. Cancer Biol Ther, 2010, 9: 507-513.
3.	Liao X, Haldar SM, Lu Y, et al. Kruppel-like factor 4 regulates pressure-induced cardiac hypertrophy. J Mol Cell Cardiol, 2010 ,49: 334-338.
4.	Rolipram attenuates bleomycin A5 -induced pulmonary fibrosis in rats. Respirology, 2009, 14: 975 -982.
5.	Todd NW, Luzina IG, Atamas SP. Molecular and cellular mechanisms of pulmonary fibrosis. Fibrogenesis Tissue Repair,2012, 5: 11.
6.	Artlett CM. Inflammasomes in wound healing and fibrosis. J Pathol, 2013, 229: 157-167 .
7.	Hu B, Wu Z, Liu T, et al. Gut-enriched Kruppel-like factor interaction with Smad3 inhibits myofibroblast differentiation. Am J Respir Cell Mol Biol, 2007 , 36: 78-84.
8.	Liu YN, Abou-Kheir W, Yin JJ, et al. Critical and reciprocal regulation of KLF4 and SLUG in transforming growth factor betainitiated prostate cancer epithelial-mesenchymal transition. Mol CellBiol, 2012 , 32: 941-953.
9.	Feinberg MW, Cao Z, Wara AK, et al. Kruppel-like factor 4 is a mediator of proinflammatory signaling in macrophages. J Biol Chem, 2005, 280: 38247 -38258.
10.	Duffield JS, Forbes SJ, Constandinou CM, et al. Selective depletion of macrophages reveals distinct, opposing roles during liver injury and repair. J Clin Invest, 2005, 115: 56-65.
11.	Liao X, Sharma N, Kapadia F, et al. Kruppel-like factor 4 regulates macrophage polarization. J Clin Invest, 2011, 121: 2736-2749.
12.	Alder JK, Georgantas RW, 3rd, Hildreth RL, et al. Kruppel-like factor 4 is essential for inflammatory monocyte differentiation in vivo. J Immunol, 2008, 180: 5645-5652.
13.	Degryse AL, Lawson WE. Progress toward improving animal models for idiopathic pulmonary fibrosis. AmJ Med Sci, 2011,341: 444-449.

1. McConnell BB, Yang VW. Mammalian Kruppel-like factors in health and diseases. Physiol Rev, 2010, 90: 1337-1381.
2. Zhou Y, Hofstetter WL, He Y, et al. KLF4 inhibition of lung cancer cell invasion by suppression of SPARC expression. Cancer Biol Ther, 2010, 9: 507-513.
3. Liao X, Haldar SM, Lu Y, et al. Kruppel-like factor 4 regulates pressure-induced cardiac hypertrophy. J Mol Cell Cardiol, 2010 ,49: 334-338.
4. Rolipram attenuates bleomycin A5 -induced pulmonary fibrosis in rats. Respirology, 2009, 14: 975 -982.
5. Todd NW, Luzina IG, Atamas SP. Molecular and cellular mechanisms of pulmonary fibrosis. Fibrogenesis Tissue Repair,2012, 5: 11.
6. Artlett CM. Inflammasomes in wound healing and fibrosis. J Pathol, 2013, 229: 157-167 .
7. Hu B, Wu Z, Liu T, et al. Gut-enriched Kruppel-like factor interaction with Smad3 inhibits myofibroblast differentiation. Am J Respir Cell Mol Biol, 2007 , 36: 78-84.
8. Liu YN, Abou-Kheir W, Yin JJ, et al. Critical and reciprocal regulation of KLF4 and SLUG in transforming growth factor betainitiated prostate cancer epithelial-mesenchymal transition. Mol CellBiol, 2012 , 32: 941-953.
9. Feinberg MW, Cao Z, Wara AK, et al. Kruppel-like factor 4 is a mediator of proinflammatory signaling in macrophages. J Biol Chem, 2005, 280: 38247 -38258.
10. Duffield JS, Forbes SJ, Constandinou CM, et al. Selective depletion of macrophages reveals distinct, opposing roles during liver injury and repair. J Clin Invest, 2005, 115: 56-65.
11. Liao X, Sharma N, Kapadia F, et al. Kruppel-like factor 4 regulates macrophage polarization. J Clin Invest, 2011, 121: 2736-2749.
12. Alder JK, Georgantas RW, 3rd, Hildreth RL, et al. Kruppel-like factor 4 is essential for inflammatory monocyte differentiation in vivo. J Immunol, 2008, 180: 5645-5652.
13. Degryse AL, Lawson WE. Progress toward improving animal models for idiopathic pulmonary fibrosis. AmJ Med Sci, 2011,341: 444-449.

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Expression and Significance of Krüppel-like Factor 4 in Experimental Pulmonary Fibrosis

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