RPEP-00080 · 1988GHK-Cu stimulated collagen synthesis in fibroblast cell cultures. The effect began at concentrations between 10 picomolar (10^-12 M) and 100 picomolar (10^-11 M), an extraordinarily low threshold.
The stimulation maximized at 1 nanomolar (10^-9 M). Above this concentration, the effect plateaued.
The collagen increase was independent of cell number changes. GHK-Cu was not simply making more cells; it was making existing cells produce more collagen.
A GHK tripeptide sequence (glycine-histidine-lysine) exists naturally within the alpha 2(I) chain of type I collagen. The authors proposed that when wounds break down collagen, proteases could release GHK fragments. These fragments would then bind copper and stimulate new collagen production at the wound site, creating a self-healing feedback loop.
Maquart, F X; Pickart, L; Laurent, M; Gillery, P; Monboisse, J C; Borel, J P · In Vitro
RPEP-00254 · 1992GHK-Cu induced dose-dependent increases in both secreted and cell-associated glycosaminoglycan synthesis by normal human fibroblasts.
Wegrowski, Y; Maquart, F X; Borel, J P · In Vitro
RPEP-00269 · 1993GHK-Cu significantly stimulated connective tissue accumulation and collagen synthesis in rat wounds in vivo, confirming its wound-healing potential first observed in cell culture.
Maquart, F X; Bellon, G; Chaqour, B; Wegrowski, J; Patt, L M; Trachy, R E; Monboisse, J C; Chastang, F; Birembaut, P; Gillery, P · Animal Study
RPEP-00316 · 1995GHK-Cu increased wound collagen (hydroxyproline), protein, DNA, and amine oxidase activity in guinea pig skin wounds, with effects requiring the peptide component, not just copper.
Buffoni, F; Pino, R; Dal Pozzo, A · Animal Study
RPEP-00420 · 1997Enkephalins directly modulate the differentiation of normal human keratinocytes in vitro, establishing opioid peptides as regulators of skin cell biology.
Nissen, J B; Kragballe, K · In Vitro
RPEP-00858 · 2003Topical BPC-157 cream reversed methylprednisolone-induced burn wound healing impairment in mice, restoring wound closure rates during concurrent steroid treatment.
Sikiric, P; Seiwerth, S; Mise, S; Staresinic, M; Bedekovic, V; Zarkovic, N; Borovic, S; Gjurasin, M; Boban-Blagaic, A; Batelja, L; Rucman, R; Anic, T · Animal Study
RPEP-00907 · 2004KPV inhibited NF-κB inflammatory signaling in human keratinocytes through a cAMP-independent mechanism, distinct from full-length alpha-MSH's classical cAMP-dependent MC1R signaling.
Elliott, Richard J; Szabo, Marika; Wagner, Mark J; Kemp, E Helen; MacNeil, Sheila; Haycock, John W · In Vitro
RPEP-01007 · 2005GHK peptide incorporated into a biotinylated collagenous wound dressing accelerated rat dermal wound healing: faster wound closure, enhanced granulation tissue formation, improved collagen deposition, and better overall histological healing scores versus scaffold alone.
Arul, V; Gopinath, D; Gomathi, K; Jayakumar, R · Animal Study
RPEP-01010 · 2005Local BPC-157 application accelerated CO2 laser wound healing in mice with faster re-epithelialization and wound contraction, extending BPC-157's documented wound healing to laser-induced tissue damage relevant to surgical and cosmetic dermatology.
Bilic, M; Bumber, Z; Blagaic, A Boban; Batelja, L; Seiwerth, S; Sikiric, P · Animal Study
RPEP-01165 · 2006Topical copper tripeptide complex (GHK-Cu) significantly accelerated healing after CO2 laser resurfacing in a double-blind, vehicle-controlled RCT, with faster re-epithelialization and improved skin quality — clinical validation of GHK-Cu for post-procedure skin recovery.
Miller, Timothy R; Wagner, Jon D; Baack, Bret R; Eisbach, Karl J · RCT
RPEP-01385 · 2008GHK-Cu and other peptide-copper complexes demonstrated measurable skin penetration and bioactive copper delivery to dermal layers, validating the bioavailability of topical copper peptide formulations for skin anti-aging and wound healing applications.
Mazurowska, Lena; Mojski, Miroslaw · In Vitro
RPEP-01402 · 2008GHK-Cu comprehensively reviewed: stimulates collagen/glycosaminoglycan synthesis, wound healing, hair growth, and reprograms gene expression (1,584 genes) toward tissue repair and anti-aging — the most versatile copper-binding tripeptide in regenerative medicine.
Pickart, Loren · Review
RPEP-04844 · 2020Itch severity in bullous pemphigoid correlates with eosinophils, substance P, neurokinin 1 receptor, IL-31 signaling, IL-13, periostin, and basophils, while mast cells and TRPV1 were not significantly correlated.
Hashimoto, Takashi; Kursewicz, Christina Dorothy; Fayne, Rachel Alison; Nanda, Sonali; Shah, Serena Maya; Nattkemper, Leigh; Yokozeki, Hiroo; Yosipovitch, Gil · Observational (Cross Sectional)
RPEP-04852 · 2020The study overturned a previous assumption. DNA was thought to be the key NET component driving inflammation in psoriasis. Instead, RNA is the critical molecule.
NET-associated RNA (naRNA), when complexed with LL-37, triggered both cytokine release and new NET formation by neutrophils through TLR8 (human) and TLR13 (mouse) receptors. This happened independently of the canonical NET component DNA.
The self-amplifying mechanism: activated neutrophils release NETs containing RNA. That RNA binds LL-37 (abundant in psoriatic skin). The complex activates more neutrophils to release more NETs with more RNA. Each cycle amplifies the inflammation.
Transferring NETs from activated neutrophils to naive (unstimulated) neutrophils triggered additional NET release, directly demonstrating the self-propagating nature of the cycle.
RNA was abundant in NETs and in psoriatic skin but not in healthy skin. This positions naRNA as a physiologically relevant NET component and a driver of chronic psoriatic inflammation.
Herster, Franziska; Bittner, Zsofia; Archer, Nathan K; Dickhöfer, Sabine; Eisel, David; Eigenbrod, Tatjana; Knorpp, Thomas; Schneiderhan-Marra, Nicole; Löffler, Markus W; Kalbacher, Hubert; Vierbuchen, Tim; Heine, Holger; Miller, Lloyd S; Hartl, Dominik; Freund, Lukas; Schäkel, Knut; Heister, Martin; Ghoreschi, Kamran; Weber, Alexander N R · Mechanistic (In Vitro + In Vivo)
RPEP-04967 · 2020CAMP transgenic mice showed increased Salmonella resistance, restored wound healing in Camp-KO skin, and topical vitamin D induced LL-37 expression with enhanced S. aureus killing in wounds.
Lowry, Malcolm B; Guo, Chunxiao; Zhang, Yang; Fantacone, Mary L; Logan, Isabelle E; Campbell, Yan; Zhang, Weijian; Le, Mai; Indra, Arup K; Ganguli-Indra, Gitali; Xie, Jingwei; Gallo, Richard L; Koeffler, H Phillip; Gombart, Adrian F · Animal
RPEP-04971 · 2020Excess dsDNA fragments triggered psoriasis-like keratinocyte changes; vitamin D blocked this via cathelicidin (CAMP), which was required for the anti-inflammatory effect.
Luo, Y; Hara, T; Kawashima, A; Ishido, Y; Suzuki, S; Ishii, N; Kambara, T; Suzuki, K · In Vitro
RPEP-04977 · 2020LL-37, defensins, S100 proteins, lipocalin 2, and RNase 7 are highly expressed in psoriatic skin and bridge innate and adaptive immune responses in disease pathogenesis.
Ma, Jing-Yi; Shao, Shuai; Wang, Gang · Review
RPEP-05031 · 2020Antimicrobial peptides LL-37, human beta-defensins, and S100A7 improve tight junction barrier function in addition to their antimicrobial activity, suggesting they could be used for barrier repair in atopic dermatitis.
Nguyen, Hai Le Thanh; Trujillo-Paez, Juan Valentin; Umehara, Yoshie; Yue, Hainan; Peng, Ge; Kiatsurayanon, Chanisa; Chieosilapatham, Panjit; Song, Pu; Okumura, Ko; Ogawa, Hideoki; Ikeda, Shigaku; Niyonsaba, François · Review
RPEP-05041 · 2020Patients developing papulopustular eruptions from EGFR monoclonal antibodies showed significant reductions in skin hBD1 and hBD3 levels, linking antimicrobial peptide suppression to drug-induced skin toxicity.
Ommori, R; Nakamura, Y; Miyagawa, F; Shobatake, C; Ogawa, K; Koyama, F; Sho, M; Ota, I; Kitahara, T; Hontsu, S; Muro, S; Asada, H · Observational
RPEP-05045 · 2020Thymosin beta-4 depletion disrupted epidermal adherens junction stability and planar cell polarity by altering perijunctional G/F-actin ratios, causing eyelid closure and hair follicle angling defects.
Padmanabhan, Krishnanand; Grobe, Hanna; Cohen, Jonathan; Soffer, Arad; Mahly, Adnan; Adir, Orit; Zaidel-Bar, Ronen; Luxenburg, Chen · Animal Study
RPEP-05057 · 2020Linear PEI/pDNA polyplexes successfully transfected human keratinocytes and fibroblasts to overexpress LL-37, with supernatants reducing S. aureus growth by 95.8%.
Patiño Vargas, Maria Isabel; Mesa Cadavid, Mónica; Arenas Gómez, Claudia Marcela; Diosa Arango, Johnatan; Restrepo Múnera, Luz Marina; Becerra Colorado, Natalia Yiset · In Vitro
RPEP-05086 · 2020Bovine lactoferrin hydrolysate achieved a minimal biofilm inhibitory concentration (MIBC) of 2.5 mg/mL against most staphylococcal strains — 4-8x lower than the minimal inhibitory concentration for direct killing. Purified peptides LFcinB and LFampin showed even lower MIBCs.
Quintieri, Laura; Caputo, Leonardo; Monaci, Linda; Cavalluzzi, Maria Maddalena; Denora, Nunzio · In Vitro
RPEP-05096 · 2020RNase 7 was significantly decreased in skin of diabetic patients with and without foot ulcers compared to healthy donors. Metformin reduced RNase 7 expression in keratinocytes in vitro, while calcitriol, phenyl butyrate, and L-isoleucine did not restore it.
Rodríguez-Carlos, Adrian; Trujillo, Valentin; Gonzalez-Curiel, Irma; Marin-Luevano, Sara; Torres-Juarez, Flor; Santos-Mena, Alan; Rivas-Santiago, Cesar; Enciso-Moreno, Jose A; Zaga-Clavellina, Veronica; Rivas-Santiago, Bruno · Observational
RPEP-05097 · 2020Coptis chinensis downregulated KLK5 and cathelicidin expression, inhibited KLK5 protease activity (reducing LL-37 processing), decreased pro-inflammatory cytokines, blocked TLR2/chitin signaling, and inhibited LL-37-induced endothelial cell proliferation.
Roh, Kyung-Baeg; Ryu, De-Hun; Cho, Eunae; Weon, Jin Bae; Park, Deokhoon; Kweon, Dae-Hyuk; Jung, Eunsun · In Vitro
RPEP-05106 · 2020Marine collagen and its derivatives (gelatin, peptides) show versatile bioactive properties including potential for tissue engineering, wound healing, dietary supplementation for weight management and glycemic control, with growing preclinical and clinical evidence.
Salvatore, Luca; Gallo, Nunzia; Natali, Maria Lucia; Campa, Lorena; Lunetti, Paola; Madaghiele, Marta; Blasi, Federica Stella; Corallo, Angelo; Capobianco, Loredana; Sannino, Alessandro · Review
RPEP-05284 · 2021Antimicrobial peptide gene expression in skin oscillates along day/night rhythms with two distinct patterns: activity-phase peptides controlled by light and sleep-phase peptides controlled by an internal circadian clock.
Bilska, Bernadetta; Zegar, Aneta; Slominski, Andrzej T; Kleszczyński, Konrad; Cichy, Joanna; Pyza, Elzbieta · Animal
RPEP-05297 · 2021Two short gecko cathelicidin-derived peptides (38-42 and 33-42 fragments) showed potent antioxidant and wound healing activity in mice with significantly lower toxicity than the parent peptide.
Cai, Shasha; Lu, Changao; Liu, Zhenlei; Wang, Wenbo; Lu, Shuxin; Sun, Zhaoxing; Wang, Guannan · Animal
RPEP-05306 · 2021AP collagen peptides blocked cortisol-induced GR activation and prevented the suppression of TGF-β signaling and collagen type I production in human dermal fibroblasts, senescent cells, and skin models.
Chae, Minjung; Bae, Il-Hong; Lim, Sung Hwan; Jung, Kyoungmi; Roh, Jonghwa; Kim, Wangi · In Vitro
RPEP-05324 · 2021MRGPRX2 acts as a broad sensor for cationic molecules, enabling mast cells to bridge nociception and skin inflammation, contributing to pruritus, pain, atopic dermatitis, and drug-induced reactions.
Corbière, Auriane; Loste, Alexia; Gaudenzio, Nicolas · Review
RPEP-05332 · 2021Both endogenous and exogenous thymosin β4 activate hair follicle cycling, promote stem cell migration and differentiation, and increase hair growth rate in animal models.
Dai, Bai; Sha, Ri-Na; Yuan, Jian-Long; Liu, Dong-Jun · Review
RPEP-05339 · 2021Cathelicidin LL37 activates mTORC1 via TLR2, and mTORC1 increases cathelicidin expression, creating a positive feedback loop driving rosacea. Topical rapamycin broke this cycle and improved patient symptoms.
Deng, Zhili; Chen, Mengting; Liu, Yingzi; Xu, San; Ouyang, Yuyan; Shi, Wei; Jian, Dan; Wang, Ben; Liu, Fangfen; Li, Jinmao; Shi, Qian; Peng, Qinqin; Sha, Ke; Xiao, Wenqin; Liu, Tangxiele; Zhang, Yiya; Zhang, Hongbing; Wang, Qian; Sun, Lunquan; Xie, Hongfu; Li, Ji · Animal + Human Observational
RPEP-05380 · 2021Cathelicidin was ~3x and HBD-2 was >6x higher in BCC patients (p<0.001). Cathelicidin >1,500 pg/mL: OR 9.9 for BCC. HBD-2 >1.2 ng/mL: OR 12.6 for BCC (p<0.001). Both showed high specificity for detecting BCC.
Fijałkowska, Marta; Kowalski, Marek; Koziej, Mateusz; Antoszewski, Bogusław · Case Control
RPEP-05667 · 2021M. restricta and M. globosa activated the NLRP3-ASC inflammasome in human keratinocytes, triggering IL-1β secretion — a key inflammatory signal. All three Malassezia species variably induced the antimicrobial peptides thymic stromal lymphopoietin, β-defensin 2, and LL-37.
Each species created a distinct inflammatory profile: M. sympodialis significantly increased IL-8 and IL-22 protein levels, while M. globosa increased CCL17 mRNA and M. restricta increased CCL22 mRNA. This species-specific pattern of inflammasome activation, cytokine release, and antimicrobial peptide induction suggests that different Malassezia species may drive the distinct clinical presentations of conditions like dandruff versus atopic dermatitis.
Park, Hye Ree; Oh, Jee Hye; Lee, Yu Jin; Park, Song Hee; Lee, Yang Won; Lee, Seongju; Kang, Hoon; Kim, Jung Eun · Basic Research
RPEP-09121 · 2024The peptide inhibitors specifically target the primary binding interface between TANGO1 and cTAGE5, two proteins required for collagen export from the endoplasmic reticulum. Treatment reduced protein levels of both TANGO1 and cTAGE5, blocking the secretion of multiple extracellular matrix components including collagens, fibrillin, and fibronectin.
In zebrafish, the peptide inhibitors altered tissue architecture and reduced granulation tissue formation during wound healing. In human dermal fibroblasts and cells from scleroderma patients (who have generalized fibrosis), the inhibitors reduced secretion of ECM proteins.
Raote, Ishier; Rosendahl, Ann-Helen; Häkkinen, Hanna-Maria; Vibe, Carina; Küçükaylak, Ismail; Sawant, Mugdha; Keufgens, Lena; Frommelt, Pia; Halwas, Kai; Broadbent, Katrina; Cunquero, Marina; Castro, Gustavo; Villemeur, Marie; Nüchel, Julian; Bornikoel, Anna; Dam, Binita; Zirmire, Ravindra K; Kiran, Ravi; Carolis, Carlo; Andilla, Jordi; Loza-Alvarez, Pablo; Ruprecht, Verena; Jamora, Colin; Campelo, Felix; Krüger, Marcus; Hammerschmidt, Matthias; Eckes, Beate; Neundorf, Ines; Krieg, Thomas; Malhotra, Vivek · In Vitro/Animal
RPEP-14218 · 2025This review maps five distinct mechanisms by which antimicrobial peptides (AMPs) promote skin wound healing beyond just killing bacteria: (1) stimulating keratinocyte migration and proliferation to close wounds, (2) promoting collagen synthesis and tissue remodeling, (3) driving angiogenesis (new blood vessel formation), (4) modulating the immune response to reduce excessive inflammation, and (5) providing broad-spectrum antimicrobial activity against bacteria, fungi, and viruses.
The review also covers structural modifications (like cyclization and amino acid substitutions) and delivery systems (hydrogels, nanoparticles) that improve AMP stability and efficacy in wound settings. Several AMPs are now in clinical trials for wound healing applications.
Wu, Yifan; Liu, Tingting; Jin, Lili; Wang, Chuyuan; Zhang, Dianbao · Review