Dataset Information

ECM-Focused Proteomic Analysis of Ear Punch Regeneration in Acomys cahirinus

ABSTRACT: In mammals, significant injury is generally followed by the formation of a fibrotic scar which provides structural integrity but fails to functionally restore damaged tissue. Spiny mice of the genus Acomys represent the first example of full skin autotomy in mammals. Acomys cahirinus has evolved extremely weak skin as a strategy to avoid predation and is able to repeatedly regenerate healthy tissue without scar after severe skin injury or full-thickness ear punches. Extracellular matrix (ECM) composition is a critical regulator of wound repair and scar formation and previous studies have suggested that alterations in its expression may be responsible for the differences in regenerative capacity observed between Mus musculus and A. cahirinus, yet analysis of this critical tissue component has been limited in previous studies by its insolubility and resistance to extraction. Here, we utilize a 2-step ECM-optimized extraction to perform proteomic analysis of tissue composition during wound repair after full-thickness ear punches in A. cahirinus and M. musculus from weeks 1 to 4 post-injury. We observe changes in a wide range of ECM proteins which have been previously implicated in wound regeneration and scar formation, including collagens, provisional matrix and coagulation proteins, and matricryptic signaling peptides. We additionally report differences in crosslinking enzyme activity and ECM protein solubility between Mus and Acomys. Furthermore, we observed rapid and sustained increases in CD206, a marker of pro-regenerative M2 macrophages, in Acomys, whereas little or no increase in CD206 was detected in Mus. Together, these findings contribute to a comprehensive understanding of tissue cues which drive the regenerative capacity of Acomys and identify a number of potential targets for future pro-regenerative therapies.

INSTRUMENT(S):

ORGANISM(S): Acomys Cahirinus Mus Musculus (mouse)

TISSUE(S): Ear

DISEASE(S): Wounds And Injuries

SUBMITTER: Maxwell McCabe

LAB HEAD: Kirk Hansen

PROVIDER: PXD047626 | Pride | 2025-10-31

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	20211129_timsTOF_EarPunch_Aco_Cell_Uninj_1_S2-A1_1_10708.d.zip	Other
	20211129_timsTOF_EarPunch_Aco_Cell_Uninj_2_S3-B5_1_10822.d.zip	Other
	20211129_timsTOF_EarPunch_Aco_Cell_Uninj_3_S3-B6_1_10823.d.zip	Other
	20211129_timsTOF_EarPunch_Aco_Cell_Uninj_4_S3-B7_1_10824.d.zip	Other
	20211129_timsTOF_EarPunch_Aco_Cell_Uninj_5_S3-B8_1_10825.d.zip	Other

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Publications

ECM-Focused Proteomic Analysis of Ear Punch Regeneration in Acomys cahirinus.

McCabe Maxwell C MC Okamura Daryl M DM Erickson Christopher B CB Perry Blair W BW Brewer Chris M CM Nguyen Elizabeth D ED Saviola Anthony J AJ Majesky Mark W MW Hansen Kirk C KC

Journal of proteome research 20250619 7

While significant acute injury leads to a functionally deficient fibrotic scar in mammals, the spiny mouse Acomys cahirinus has evolved scar-free regeneration of severely damaged tissue. Extracellular matrix (ECM) composition is a critical regulator of wound repair, and previous studies have suggested that alterations in its expression may be responsible for the differences in regenerative capacity observed between Mus musculus and A. cahirinus, yet analysis of this critical ...[more]

PMID: 40534468

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Project description:While considerable progress has been made towards understanding the complex processes and pathways that regulate human wound healing, regenerative medicine has been unable to develop therapies that coax the natural wound environment to heal scar-free. The inability to induce perfect skin regeneration stems partly from our limited understanding of how scar-free healing occurs in a natural setting. Here we have investigated the wound repair process in adult axolotls and demonstrate that they are capable of perfectly repairing full thickness excisional wounds made on the flank. In the context of mammalian wound repair, our findings reveal a substantial reduction in hemostasis, reduced neutrophil infiltration and a relatively long delay in production of new extracellular matrix (ECM) during scar-free healing. Additionally, we test the hypothesis that metamorphosis leads to scarring and instead show that terrestrial axolotls also heal scar-free, albeit at a slower rate. Analysis of newly forming dermal ECM suggests that low levels of fibronectin and high levels of tenascin-C promote regeneration in lieu of scarring. Lastly, a genetic analysis during wound healing comparing epidermis between aquatic and terrestrial axolotls suggests that matrix metalloproteinases may regulate the fibrotic response. Our findings outline a blueprint to understand the cellular and molecular mechanisms coordinating scar-free healing that will be useful towards elucidating new regenerative therapies targeting fibrosis and wound repair. We used microarray analysis to determine the gene expression changes that take place during scar free wound healing in aquatic and terrestrial axolotl salamanders. Epidermal tissue was harvested using a 4mm biopsy punch. Two wounds were made along the flank and posterior to the forelimbs. Harvested epidermis was pooled for each animal. Four biological replicates were collected from uninjured epidermis (D0) and at 1, 3, and 7 days post injury.

Dataset Information

ECM-Focused Proteomic Analysis of Ear Punch Regeneration in Acomys cahirinus

Dataset's files

Publications

ECM-Focused Proteomic Analysis of Ear Punch Regeneration in <i>Acomys cahirinus</i>.

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Dataset Information

ECM-Focused Proteomic Analysis of Ear Punch Regeneration in Acomys cahirinus

Dataset's files

Publications

ECM-Focused Proteomic Analysis of Ear Punch Regeneration in &lt;i&gt;Acomys cahirinus&lt;/i&gt;.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

ECM-Focused Proteomic Analysis of Ear Punch Regeneration in <i>Acomys cahirinus</i>.