Reversal of Emphysema-Related Lung Destruction?

Emphysema-Related Lung Destruction and its Reversal by GHK (Genome Medicine)

EXCERPT: "Treatment of human fibroblasts with GHK recapitulated TGFβ-induced gene-expression patterns, led to the organization of the actin cytoskeleton, and elevated the expression of integrin β1. Furthermore, addition of GHK or TGFβ restored collagen I contraction and remodeling by fibroblasts derived from COPD lungs compared to fibroblasts from former smokers without COPD...

Furthermore, [it was shown] that by treating distal lung fibroblasts from COPD patients with GHK, we can restore normal contractile function through re-organization of the actin cytoskeleton and up-regulation of integrin-β1. These data further support the potential of GHK as a therapeutic in the treatment of emphysema."

Read the full article at: https://genomemedicine.biomedc...ticles/10.1186/gm367


Biochemist (and discoverer of GHK) Dr. Loren Pickart, provides further information, comments, and ideas at:


Dr. Loren Pickart who has a BA in Chemistry and Mathematics from the University of Minnesota and a PhD in Biochemistry from the University of California, San Francisco is dedicated to the research and further discussion of biochemistry, science, and health in all its applications.


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Original Post

There are new reports of lung protection by GHK. 

1. .2016 Sep 6; 7(36): 58405–58417.Published online 2016 Aug 10. doi:  10.18632/oncotarget.11168 PMCID: PMC5295439The tri-peptide GHK-Cu complex ameliorates lipopolysaccharide-induced acute lung injury in mice

Jeong-Ran Park,1,2 Hanbyeol Lee,1 Seok-In Kim,3 and Se-Ran Yang1Oncotarget

The tripeptide-copper complex glycyl-l-histidyl-l-lysine-Cu (II) (GHK-Cu) is involved in wound healing and tissue remodeling. Although GHK-Cu exhibits anti-aging and tissue renewing properties, its roles in acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) are still unknown. Therefore, we examined the effects of GHK-Cu in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages in vitroand ALI in mice in vivo. GHK-Cu treatment reduced reactive oxygen species (ROS) production, increased superoxide dismutase (SOD) activity while decreased TNF-α and IL-6 production through the suppression of NF-κB p65 and p38 MAPK signaling in vitro and in vivo model of ALI. Moreover, GHK-Cu attenuated LPS-induced lung histological alterations, suppressed the infiltration of inflammatory cells into the lung parenchyma in LPS-induced ALI in mice. Taken together, these findings demonstrate that GHK-Cu possesses a protective effect in LPS-induced ALI by inhibiting excessive inflammatory responses; accordingly it may represent a novel therapeutic approach for ALI/ARDS.

2. Front. Pharmacol., 12 December 201

GHK Peptide Inhibits Bleomycin-Induced Pulmonary Fibrosis in Mice by Suppressing TGFβ1/Smad-Mediated Epithelial-to-Mesenchymal Transition

Xiao-Ming Zhou ,Gui-Liang Wang , Xiao-Bo Wang, Li Liu, Qin Zhang, Yan Yin, Qiu-Yue Wang, Jian Kang and Gang Hou


GHK-Cu Elicits in Vitro, Dose-Dependent Transcriptional Alterations In Pathways Relevant ToExtracellular Matrix Composition

R. McMurry, C. Perdomo, G. Liu, S. Zhang, C. Stevenson, J. Campbell, A. Spira, M. Lenburg

Computational Biomedicine, Boston University School of Medicine, Boston, MA Disease Interception Accelerator, Janssen Pharmaceutical Companies of Johnson & Johnson, London, NJ, United KingdomRationale: The lack of disease-modifying interventions in COPD represents a critically unmet medical need, the resolution of which could reduce mortality and improve quality of life for millions of Americans. A meta-analysis of gene expression signatures associated with emphysema and COPO identified the tripeptide GHK (glycyl-Lhistidy14.-lysine) as a candidate drug likely to reverse disease-associated gene expression. Consistent with this hypothesis, GHK-Cu reverses collagen-remodeling deficits present in lung fibroblasts from COPD patients. Motivated by these findings, we sought to more fully characterize the transcriptional effects of GHK in human lung fibroblasts to gain insights into GHKS mechanisms of action.

Methods: Human fetal lung fibroblasts (HFL I) were treated for 6, 12, 24, or 48 hours with either phosphate buffered saline. GHK-Cu (0.1nM, 1nM or 10 nML or copper acetate at a concentration equivalent to that found in the 10nM dose of GHK-Cu. RNA was isolated from the samples and hybridized to Hu 1.0ST microarrays for gene expression profiling. Within each time point, a Spearman correlation was employed to identify genes whose expression is dose-dependent to GHK-Cu. Genes were also ranked according to this correlation and analyzed for functional enrichment via Gene Set Enrichment Analysis (GSEA).

Results: We identified a signature of 329 genes with dose-responsive expression to GHK-Cu at 48 hours (q<0.05). Notably, the 238 genes whose expression is decreased with increasing GHK-Cu dose are involved with collagen fibril assembly (q< 0.001) while the upregulated genes are involved with adherens junctions and cell division (q <0.001). Additionally, we find that genes with the most dose-responsive increases in transcription after 6 hours GHK-Cu treatment are disproportionately associated with the metabolism of glycosaminoglycans.

Conclusions: GHK-Cu elicits alterations in pathways relevant to the extracellular matrix (EM) within lung fibroblasts at early and late time points. Given the dysregulation of EM in emphysema, future work is warranted to clarify the mechanisms by which GHK-Cu induces these gene expression alterations and restores collagen remodeling in order to better understand its potential as a COPD therapeutic.

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