Kisspeptin-10 regulates glycosaminoglycan and decorin content in human cardiac fibroblast cultures

Kisspeptin-10 increased glycosaminoglycan and decorin levels in cultured human cardiac fibroblasts, acting through GPR54 and FAK signalling for the glycosaminoglycan response. The glycosaminoglycan increase was dose-dependent and blocked by GPR54 or FAK inhibitors, while decorin secretion rose without a change in expression. These findings suggest kisspeptin-10 may participate in cardiac extracellular matrix remodelling.

Journal article — in vitro experimental study. Population: human cardiac fibroblast cell line. Interventions: Kisspeptin-10 (KiSS-10); peptide 234 (GPR54 blocker); FAK inhibitor 14 (FAKi); D609 (phospholipase C inhibitor).

KiSS-10 treatment caused a dose-dependent increase in glycosaminoglycan content in both cells and medium. This effect was abolished by GPR54 blockade with peptide 234 or FAK inhibition with FAKi, but D609 did not alter glycosaminoglycan levels relative to KiSS-10 alone. KiSS-10 also increased decorin secretion without changing decorin expression, and peptide 234 did not affect media decorin compared with KiSS-10 alone.

This paper expands kisspeptin biology beyond reproduction by showing that KiSS-10 can alter extracellular matrix components in human cardiac fibroblasts through GPR54 and FAK signalling. It does not establish whether kisspeptin-10 has this effect in living hearts, what the downstream decorin mechanism is, or any therapeutic implication.

Key findings

• KiSS-10 increased glycosaminoglycan content in both cells and medium in a dose-dependent manner.
• Blocking GPR54 with peptide 234 or FAK with FAKi abolished the KiSS-10-induced increase in glycosaminoglycan content.
• Inhibiting phospholipase C with D609 did not change glycosaminoglycan levels compared with KiSS-10 alone.
• KiSS-10 increased decorin secretion but not decorin expression.
• Adding peptide 234 to KiSS-10 did not alter media decorin levels compared with KiSS-10 alone.

Limitations

• Authors did not report limitations.
• In vitro findings in a cell line may not reflect primary human cardiac fibroblasts or intact heart tissue.
• No in vivo model was used, so physiological or clinical relevance is not established.
• The mechanism by which decorin secretion increased without increased expression was not addressed.

The record

• Journal: Pharmacological reports : PR 78(4): 1179-1191
• Published: 2026-05-20
• PMID: 42159865 — DOI: 10.1007/s43440-026-00870-6
• MeSH terms: Myocardium, Cells, Cultured, Cell Line, Extracellular Matrix, Fibroblasts, Humans, Glycosaminoglycans, Receptors, G-Protein-Coupled, Signal Transduction, Dose-Response Relationship, Drug, Decorin, Kisspeptins
• Funding: Uniwersytet Medyczny w Lodzi; Narodowe Centrum Nauki
• Author countries: Poland

Peptide profiles: Kisspeptin.

All indexed evidence: Kisspeptin trials & papers.

Related studies: Neurotransmitter and neuromodulator imbalance in kisspeptin/GnRH regulation in rodent…, Chronic subcutaneous kisspeptin-10 stimulates gonadotropin secretion for 12 days in…, Dlk1-deficient mice achieve puberty despite low body weight and low levels of leptin and…, Kisspeptin System: A Modulator of Neuroinflammation and Behaviour in Temporal Lobe….