Published findings, in context.

Isolated rat aorta and cultured endothelial cells: vasomotor tone and Src–caveolin-1–eNOS signaling

“Modulatory effects of BPC 157 on vasomotor tone and the activation of Src-Caveolin-1-endothelial nitric oxide synthase pathway.”

Hsieh MJ, Lee CH, Chueh HY et al.·Scientific Reports·2020·PMID 33051481 (opens PubMed in a new tab)·DOI 10.1038/s41598-020-74022-y (opens the publisher record in a new tab)

Filed under BPC-157

Model

Ex vivo rat aortic rings with and without endothelium; 3D vascular smooth muscle cell model; cultured endothelial cells

Exposure

BPC-157 vs no-peptide preparations (ex vivo and in vitro)

Comparator

Preparations without peptide; L-NAME, hemoglobin, Src inhibitor

In isolated rat aorta, concentration-dependent vasodilation was observed that was attenuated in the absence of endothelium and inhibited by L-NAME or hemoglobin, indicating a nitric oxide-dependent mechanism. In endothelial cells, nitric oxide generation and phosphorylation of Src, caveolin-1 and eNOS increased and were abolished by a Src inhibitor, with less caveolin-1/eNOS association in co-immunoprecipitation assays. No direct relaxant effect on smooth muscle cells was seen in the 3D model.

Rat Achilles-derived fibroblasts: GHR gene and protein expression, proliferation and JAK2 signaling

Chang CH, Tsai WC, Hsu YH et al.·Molecules·2014·PMID 25415472 (opens PubMed in a new tab)Title on PubMed·DOI 10.3390/molecules191119066 (opens the publisher record in a new tab)

Filed under BPC-157

Model

Primary fibroblasts isolated from rat Achilles; cDNA microarray, quantitative PCR, Western blot

Exposure

BPC-157, with and without subsequent GHR-ligand stimulation, vs no-peptide culture

Comparator

Culture without peptide

Microarray analysis identified GHR among the most strongly induced genes in Achilles-derived fibroblasts exposed to the peptide; the concentration- and time-dependent increase was confirmed at the mRNA and protein levels. Subsequent stimulation of pre-exposed cells with the GHR ligand was associated with greater proliferation (MTT, PCNA) and JAK2 activation. In vitro observation whose in vivo relevance was not assessed.

Human lung tissue gene-expression profiling, a Connectivity Map query and cultured lung fibroblasts exposed to GHK

“A gene expression signature of emphysema-related lung destruction and its reversal by the tripeptide GHK”

Campbell JD, McDonough JE, Zeskind JE, et al.·Genome Medicine·2012·PMID 22937864 (opens PubMed in a new tab)·DOI 10.1186/gm367 (opens the publisher record in a new tab)

Filed under GHK-Cu

Model

Gene-expression profiling of 64 lung tissue samples from 8 lungs of smokers with COPD; computational query of the Connectivity Map; in vitro exposure of lung fibroblasts from individuals with COPD and from former smokers without COPD to the GHK tripeptide (without copper)

Exposure

GHK tripeptide vs unexposed lung fibroblast cultures

Comparator

Unexposed fibroblasts; TGF-β as positive control

The authors identified 127 genes associated with regional emphysema severity. Using the Connectivity Map, GHK was identified as a compound predicted to reverse that gene signature and to induce patterns consistent with activation of the TGF-β pathway. In human fibroblasts, GHK reproduced TGF-β-induced expression patterns, organized the actin cytoskeleton, increased integrin β1 and restored the capacity of fibroblasts derived from COPD lungs to contract and remodel a three-dimensional gel in culture. The authors emphasized the need for further studies on the mechanism and on COPD progression.

Rat Achilles explants and Achilles-derived fibroblasts: outgrowth, survival, migration and FAK–paxillin signaling

Chang CH, Tsai WC, Lin MS et al.·Journal of Applied Physiology·2011·PMID 21030672 (opens PubMed in a new tab)Title on PubMed·DOI 10.1152/japplphysiol.00945.2010 (opens the publisher record in a new tab)

Filed under BPC-157

Model

Explant cultures of rat Achilles and primary rat Achilles-derived fibroblasts

Exposure

BPC-157 vs no-peptide culture

Comparator

Culture without peptide

In rat Achilles explants, cell outgrowth was faster; fibroblast proliferation (MTT) did not change, but survival under H2O2 stress, transwell migration and cell spreading increased in a concentration-dependent manner, with F-actin formation and higher FAK and paxillin phosphorylation and no change in total protein. The authors propose the FAK–paxillin pathway as a mechanistic hypothesis.

Dermal fibroblast cultures: MMP-2, TIMP-1 and TIMP-2 with GHK-Cu, copper ions and copper-free GHK

Life Sciences·2000·PMID 11045606 (opens PubMed in a new tab)Full record on PubMed·DOI 10.1016/s0024-3205(00)00803-1 (opens the publisher record in a new tab)

Filed under GHK-Cu

Model

Dermal fibroblast cultures; measurement of MMP-2, TIMP-1 and TIMP-2 in conditioned media

Exposure

GHK-Cu vs copper ions alone vs copper-free GHK tripeptide

Comparator

Control cultures; copper-free GHK; copper ions alone

GHK-Cu increased MMP-2 levels and MMP-2 mRNA in cultured fibroblasts and increased the secretion of TIMP-1 and TIMP-2. The effect on MMP-2 was reproduced by copper ions but not by the copper-free GHK tripeptide, pointing to a substantial contribution of the metal to the observed activity.

Normal human fibroblast cultures: synthesis of sulfated glycosaminoglycans and hyaluronic acid

“Stimulation of sulfated glycosaminoglycan synthesis by the tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu2+”

Wegrowski Y, Maquart FX, Borel JP·Life Sciences·1992·PMID 1522753 (opens PubMed in a new tab)·DOI 10.1016/0024-3205(92)90504-i (opens the publisher record in a new tab)

Filed under GHK-Cu

Model

Normal human fibroblast cultures; labeling with tritiated glucosamine and 35S-sulfate to quantify glycosaminoglycans

Exposure

GHK-Cu vs no-GHK-Cu culture

Comparator

Control cultures without GHK-Cu

GHK-Cu induced a biphasic, concentration-dependent increase in total glycosaminoglycan synthesis, with a maximum in the nanomolar range; at higher concentrations, synthesis returned to control levels. It preferentially increased the synthesis of extracellular dermatan sulfate and cell-layer-associated heparan sulfate, without affecting hyaluronic acid synthesis.

Fibroblast cultures: protein synthesis and cell number across GHK-Cu concentrations

Maquart FX, Pickart L, Laurent M, et al.·FEBS Letters·1988·PMID 3169264 (opens PubMed in a new tab)Title on PubMed·DOI 10.1016/0014-5793(88)80509-x (opens the publisher record in a new tab)

Filed under GHK-Cu

Model

Fibroblast cultures exposed to a range of GHK-Cu concentrations; measurement of protein synthesis and cell number

Exposure

GHK-Cu vs no-GHK-Cu culture

Comparator

Control cultures without GHK-Cu

Protein synthesis by cultured fibroblasts was measured across a range of GHK-Cu concentrations, from picomolar to nanomolar, together with cell number, which did not change. The protein measured and the direction of the result are described in the original record. The authors noted that the Gly-His-Lys sequence occurs in the α2(I) chain of type I procollagen and proposed it as a possible physiological origin of the peptide.

Normal and neoplastic liver cells in culture: survival and growth with a tripeptide from human serum

Pickart L, Thaler MM·Nature New Biology·1973·PMID 4349963 (opens PubMed in a new tab)Title on PubMed

Filed under GHK-Cu

Model

Normal and neoplastic liver cells in culture exposed to a tripeptide from human serum; design details are not available in the indexed record

Exposure

Tripeptide from human serum

Discovery work for the GHK tripeptide. The authors described a tripeptide in human serum that prolonged the survival of normal liver cells in culture and increased the growth of neoplastic liver cells. PubMed has no abstract for this record, so the cell source, design and quantitative details could not be verified.