HLF provide an excellent model system to study many aspects of human pulmonary function and pathophysiology.
HLF from Cell Applications, Inc. have been utilized in a number of research publications, for example to:
- demonstrate differential gene expression patterns between fetal and adult lung fibroblasts, in particular showing that fetal fibroblasts express higher level of TGF-β receptor interacting protein 1 (TRIP-1) and consequently are less able to contract collagen than adult lung fibroblasts, leading to better healing of acute injuries in very immature lungs compared to higher levels of fibrosis observed in older patients (Navarro, 2009), and additionally discover that TRIP-1 regulates lung fibroblast/myofibroblast trans-differentiation (Nyp, 2014);
- show that angiotensin II promotes lung fibrosis by activating expression of IL-4, IL-7, and PDGF-D increasing the extracellular matrix formation, and that this process can be blocked by angiotensin receptor inhibitor candesartan (Okada, 2009);
- determine that phosphorylation of C/EBPβ contributes to lung fibrosis (Buck, 2011);
- demonstrate that increased tissue rigidity activates toll-like receptor 2 and NF-κB in lung fibroblasts and induces expression of cytokines, CXCL1-3, IL-8 and TNF-α (Zheng, 2011);
- demonstrate that 2-ethoxyestradiol, a non-estrogenic estradiol metabolite analog, inhibits cell growth and retards the progression of pulmonary fibrosis and hypertension (Tofovic, 2008, 2009);
- identify the hypoxia-induced ROS/RhoA–ROCK dependent actin reorganization as a mediator of myofibroblast transformation and collagen synthesis in lung fibrosis (Ni, 2013).
Normal human lung parenchyma. Each lot is tested negative for HIV, Hepatitis B, Hepatitis C, mycoplasma, bacteria, and fungi.
1st passage, >500,000 cells in Basal Medium containing 10% FBS & 10% DMSO.
Ampoule of cryopreserved HLF (506-05a or 506-05f), 500 ml of Fibroblast Growth Medium (116-500), and a Subculture Reagent Kit (090K).
Shipped in Growth Medium at 2nd passage in either flasks or multiwell dishes.
Can be cultured at least 12 doublings.
Nyp, M., A. Navarro, M. Rezaiekhaligh, R. Perez, S. Mabry, and I. Ekekezie. 2014. TRIP-1 via AKT modulation drives lung fibroblast/myofibroblast trans-differentiation. Respiratory Research. 15:19.
Ni, J., Z. Dong, W. Han, D. Kondrikov, and Y. Su. 2013. The role of RhoA and cytoskeleton in myofibroblast transformation in hyperoxic lung fibrosis. Free Radical Biology and Medicine. 61:26-39.
Buck, M., and M. Chojkier. 2011. C/EBPβ-Thr217 Phosphorylation Signaling Contributes to the Development of Lung Injury and Fibrosis in Mice. PloS one. 6:e25497.
Zheng, M., D.M. Jones, C. Horzempa, A. Prasad, and P.J. McKeown-Longo. 2011. The first type III domain of fibronectin is associated with the expression of cytokines within the lung tumor microenvironment. Journal of Cancer. 2:478.
Navarro, A., M. Rezaiekhaligh, J.A. Keightley, S.M. Mabry, R.E. Perez, and I.I. Ekekezie. 2009. Higher TRIP-1 level explains diminished collagen contraction ability of fetal versus adult fibroblasts. American Journal of Physiology - Lung Cellular and Molecular Physiology. 296:L928-L935.
Okada, M., K. Suzuki, M. Matsumoto, K. Takada, T. Nakanishi, H. Horikoshi, T. Higuchi, Y. Hosono, M. Nakayama, and F. Ohsuzu. 2009. Effects of angiotensin on the expression of fibrosis-associated cytokines, growth factors, and matrix proteins in human lung fibroblasts. Journal of Clinical Pharmacy and Therapeutics. 34:289-299.
Tofovic, S.P., X. Zhang, E.K. Jackson, H. Zhu, and G. Petrusevska. 2009. 2-methoxyestradiol attenuates bleomycin-induced pulmonary hypertension and fibrosis in estrogen-deficient rats. Vascular pharmacology. 51:190-197.
Tofovic, S.P., X. Zhang, H. Zhu, E.K. Jackson, O. Rafikova, and G. Petrusevska. 2008. 2-Ethoxyestradiol is antimitogenic and attenuates monocrotaline-induced pulmonary hypertension and vascular remodeling. Vascular pharmac. 48:174-183.
Ikeda, J.,, Y. Okada, H., Sakai, and H. Osuga. 2003. Anti-neurodegenerative agents. Patent Applications US 20050261306 A1.
Leung, K.H., V. Pippalla, A. Kreutter, and M. Chandler. 1998. Functional effects of FGF-13 on human lung fibroblasts, dermal microvascular endothelial cells, and aortic smooth muscle cells. Biochem. & Biophys. Research Communic. 250:137-142.