Next-generation personalized drug discovery: the tripeptide GHK hits center stage in chronic obstructive pulmonary disease
Open accessAbstract
Chronic lung diseases (CLDs), including chronic obstructive pulmonary disease (COPD), are the second leading cause of death worldwide. The first report of database-driven drug discovery in carefully phenotyped COPD specimens has now been published in Genome Medicine, combining gene expression data in defined emphysematous areas with connectivity-map-based compound discovery. This joint effort may lead the way to novel and potentially more efficient concepts of personalized drug discovery for COPD in particular, and CLD in general. See research article http://genomemedicine.com/content/4/8/67/abstract.
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Lung fibroblasts from COPD patients treated with GHK or TGF-β both restored function, and they had elevated expression of integrin beta 1.
“Lung fibroblasts from COPD patients, which had impaired ability to contract and restructure collagen, were treated with GHK or TGF-β. Both molecules restored function of fibroblasts. They also had an elevated expression of integrin beta 1 [37,38].”
From Regenerative and Protective Actions of the GHK-Cu Peptide in the Light of the New Gene Data (2018) · cites this paper as [38]
The 'Unbiased identification of new drugs' section (page unavailable) says GHK partially reversed emphysema-associated phenotypes in fibroblasts from COPD patients. It does not report that both GHK and TGF-β restored fibroblast function, or that integrin beta 1 expression increased; the 'Definition of a strong disease signature' section discusses TGF-β signaling but not those treatment outcomes. (LLM, conf=0.88)
Experimental — accuracy not yet measuredA study demonstrated that GHK can reverse expression of key genes in a COPD gene signature: 127 genes were altered in COPD patients, more severe emphysema correlated with degree of change, inflammatory genes were upregulated and tissue remodeling/repair genes downregulated, and GHK reversed changes associated with emphysematous destruction, including decreased TGF-β pathway activity, to activation
“This is evident from a study which demonstrated GHK’s ability to reverse expression of key genes, included in a gene signature of COPD—Chronic Obstructive Pulmonary Disease. The expression of 127 genes was altered in COPD patients. More severe emphysema symptoms were correlated with the degree of change in gene expression. Genes whose expression was associated with inflammation were upregulated,”
From Regenerative and Protective Actions of the GHK-Cu Peptide in the Light of the New Gene Data (2018) · cites this paper as [38]
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Experimental — accuracy not yet measuredThe Broad Institute Connectivity Map is a reliable tool allowing prediction of biological actions of various compounds.
“In this study, it was confirmed that the Broad Institute Connectivity Map is a reliable tool allowing prediction of biological actions of various compounds.”
From Modulation of Gene Expression in Human Breast Cancer MCF7 and Prostate Cancer PC3 Cells by the Human Copper-Binding Peptide GHK-Cu (2021) · cites this paper as [4]
The ‘Unbiased identification of new drugs’ section describes CMap as a screening tool that connects compounds with potential biological effects, and ‘Future directions’ says studies have shown its feasibility for identifying therapeutics and predicting side effects. The paper does not establish that its predictions are generally reliable; the GHK result described there was only partially validated in vitro. (LLM, conf=0.82)
Experimental — accuracy not yet measuredBeneficial gene effects of GHK, discovered through the Connectivity Map, correlate with its effects in vitro.
“It was confirmed that beneficial gene effects of GHK, discovered through the computer-based tool The Connectivity Map, correlate with its effects in vitro.”
From Modulation of Gene Expression in Human Breast Cancer MCF7 and Prostate Cancer PC3 Cells by the Human Copper-Binding Peptide GHK-Cu (2021) · cites this paper as [4]
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Cites
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A gene expression signature of emphysematous lung destruction and its reversal by the tripeptide GHK
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Cited by
Sorted by citations
Regenerative and Protective Actions of the GHK-Cu Peptide in the Light of the New Gene Data
Pickart, L., & Margolina, A. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19071987 · Cited by 158 · see citing works
GHK Peptide as a Natural Modulator of Multiple Cellular Pathways in Skin Regeneration
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- Authors
- Meiners, S., & Eickelberg, O.
- Affiliations
- Helmholtz Munich (DE)
- Corresponding author
- Eickelberg, Oliver
- Venue
- Genome Medicine
- Published
- 2012
- Volume
- 4
- Issue
- 9
- Pages
- 70
- ISSN
- 1756-994X (ISSN-L)
- PMC
- PMC3580440
- OpenAlex
- W2145612353
- Cited by
- 10
- References
- 3
- Citations by year
- 2023: 1 · 2022: 1 · 2021: 2 · 2020: 2 · 2019: 1 · 2018: 1 · 2015: 1 · 2014: 1
- FWCI
- 0.69
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Genome Medicine (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Open access LMU (Ludwid Maxmilian's Universitat Munchen) (submittedVersion)
- Site cant be reached (submittedVersion)
- Topics
- Physical Sciences › Computer Science › Computational Theory and Mathematics › Computational Drug Discovery Methods
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Chronic Obstructive Pulmonary Disease (COPD) Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bioinformatics and Genomic Networks
- Keywords
- chronic obstructive pulmonary disease, emphysema, gene expression profiling, Connectivity Map, chronic lung disease
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