A synthetic connexin 43 mimetic peptide augments corneal wound healing. 2013

Keith Moore, and Zachary J Bryant, and Gautam Ghatnekar, and Udai P Singh, and Robert G Gourdie, and Jay D Potts
University of South Carolina School of Medicine, 6439 Garners Ferry Rd., Columbia, SC 29209, USA. Electronic address: moorekb@email.sc.edu.

The ability to safely and quickly close wounds and lacerations is an area of need in regenerative medicine, with implications toward healing a wide range of tissues and wounds. Using an in vivo corneal injury model, our study applied a newly developed peptide capable of promotion of wound healing and epithelial regeneration. The alpha-carboxy terminus 1 (αCT1) peptide is a 25 amino acid peptide from the C-terminus of connexin 43 (Cx43), modified to promote cellular uptake. Previous studies applying αCT1 to excisional skin wounds in porcine models produced tissues having an overall reduced level of scar tissue and decreased healing time. Rapid metabolism of αCT1 in previous work led to the investigation of extended release on wound healing rate used in this study. Here we delivered αCT1 both directly, in a concentrated pluronic solution, and in a sustained system, using polymeric alginate-poly-l-ornithine (A-PLO) microcapsules. Cell toxicity analysis showed minimal cell-loss with microcapsule treatment. Measurement of wound healing using histology and fluorescence microscopy indicated significant reduction in healing time of αCT1 microcapsule treated rat corneas compared with controls (88% vs. 38%). RT-PCR analysis showed an initial up regulation followed by down regulation of the gene keratin-19 (Krt19). Zonula occludens 1 (ZO-1) showed an opposite down regulation followed by an up regulation whereas Cx43 showed a biphasic response. Inflammatory indexes demonstrated a reduction in the inflammation of corneas treated with αCT1 microcapsules when compared with pluronic gel vehicle. These results suggest αCT1, when applied in a sustained release system, acts as a beneficial wound healing treatment.

UI MeSH Term Description Entries
D008297 Male Males
D008856 Microscopy, Fluorescence Microscopy of specimens stained with fluorescent dye (usually fluorescein isothiocyanate) or of naturally fluorescent materials, which emit light when exposed to ultraviolet or blue light. Immunofluorescence microscopy utilizes antibodies that are labeled with fluorescent dye. Fluorescence Microscopy,Immunofluorescence Microscopy,Microscopy, Immunofluorescence,Fluorescence Microscopies,Immunofluorescence Microscopies,Microscopies, Fluorescence,Microscopies, Immunofluorescence
D010446 Peptide Fragments Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques. Peptide Fragment,Fragment, Peptide,Fragments, Peptide
D002214 Capsules Hard or soft soluble containers used for the oral administration of medicine. Capsule,Microcapsule,Microcapsules
D004195 Disease Models, Animal Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases. Animal Disease Model,Animal Disease Models,Disease Model, Animal
D005131 Eye Injuries Damage or trauma inflicted to the eye by external means. The concept includes both surface injuries and intraocular injuries. Injuries, Eye,Eye Injury,Injury, Eye
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D012333 RNA, Messenger RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm. Messenger RNA,Messenger RNA, Polyadenylated,Poly(A) Tail,Poly(A)+ RNA,Poly(A)+ mRNA,RNA, Messenger, Polyadenylated,RNA, Polyadenylated,mRNA,mRNA, Non-Polyadenylated,mRNA, Polyadenylated,Non-Polyadenylated mRNA,Poly(A) RNA,Polyadenylated mRNA,Non Polyadenylated mRNA,Polyadenylated Messenger RNA,Polyadenylated RNA,RNA, Polyadenylated Messenger,mRNA, Non Polyadenylated
D014945 Wound Healing Restoration of integrity to traumatized tissue. Healing, Wound,Healings, Wound,Wound Healings
D015536 Down-Regulation A negative regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins. Receptor Down-Regulation,Down-Regulation (Physiology),Downregulation,Down Regulation,Down-Regulation, Receptor

Related Publications

Keith Moore, and Zachary J Bryant, and Gautam Ghatnekar, and Udai P Singh, and Robert G Gourdie, and Jay D Potts
October 2016, British journal of pharmacology,
Keith Moore, and Zachary J Bryant, and Gautam Ghatnekar, and Udai P Singh, and Robert G Gourdie, and Jay D Potts
June 2018, International journal of molecular sciences,
Keith Moore, and Zachary J Bryant, and Gautam Ghatnekar, and Udai P Singh, and Robert G Gourdie, and Jay D Potts
January 2009, Journal of postgraduate medicine,
Keith Moore, and Zachary J Bryant, and Gautam Ghatnekar, and Udai P Singh, and Robert G Gourdie, and Jay D Potts
March 2023, Acta biomaterialia,
Keith Moore, and Zachary J Bryant, and Gautam Ghatnekar, and Udai P Singh, and Robert G Gourdie, and Jay D Potts
August 2010, Pflugers Archiv : European journal of physiology,
Keith Moore, and Zachary J Bryant, and Gautam Ghatnekar, and Udai P Singh, and Robert G Gourdie, and Jay D Potts
July 2015, Journal of dermatological science,
Keith Moore, and Zachary J Bryant, and Gautam Ghatnekar, and Udai P Singh, and Robert G Gourdie, and Jay D Potts
January 2015, PloS one,
Keith Moore, and Zachary J Bryant, and Gautam Ghatnekar, and Udai P Singh, and Robert G Gourdie, and Jay D Potts
June 2009, Tissue engineering. Part A,
Keith Moore, and Zachary J Bryant, and Gautam Ghatnekar, and Udai P Singh, and Robert G Gourdie, and Jay D Potts
April 2011, Journal of cellular and molecular medicine,
Keith Moore, and Zachary J Bryant, and Gautam Ghatnekar, and Udai P Singh, and Robert G Gourdie, and Jay D Potts
November 2019, Journal of cellular physiology,
Copied contents to your clipboard!