# Regulation of Embryonic Wound Healing by Matrix Metalloproteinases in Xenopus laevis Tailbud Stage

**Authors:** Daniel Kraus, Paulina Kikinderova, Pavel Abaffy, Dominika Kadlcikova, Ravindra Naraine, Radek Sindelka

PMC · DOI: 10.1111/wrr.70134 · Wound Repair and Regeneration · 2026-02-18

## TL;DR

This study explores how matrix metalloproteinases help in scarless wound healing in Xenopus embryos and shows that this process is similar in mammals.

## Contribution

The study identifies specific MMPs and the AP-1 stress response as key regulators of embryonic wound healing in Xenopus.

## Key findings

- MMPs 1, 7, 8, and 9 are expressed during the intermediate phase of wound healing in Xenopus.
- MMP expression depends on the stress response mediated by the AP-1 transcription factor.
- The findings correlate with mammalian wound healing, suggesting a conserved biological process.

## Abstract

Scarless wound healing remains a key goal in regenerative research. However, the gene regulatory networks and mechanisms behind this process are still not fully understood, despite the use of high‐throughput analyses and various research models. In our study, we focus on the intermediate phase and examine the role of remodelling genes called matrix metalloproteinases (MMPs) in the 
Xenopus laevis
 model. Through temporal bulk RNA‐Seq analysis, we identified the fos/jun (AP‐1) combination expressed during the early phase and four main mmps (1, 7, 8, and 9) expressed during the intermediate phase of healing. Using specific MMP inhibitors and morpholino‐oligonucleotides targeting fos/jun, we found that mmp expression depends on stress response and that they are crucial for embryonic wound healing. We also analysed other published healing data sets (single cell and bulk RNA‐Seq) and observed a strong correlation of our observations with healing in mammals. In summary, our study indicates that wound healing is a conserved biological process that begins with a stress response involving AP‐1. It then progresses through the stage of extensive healing activity, including the expression induction of specific mmp genes during the remodelling phase.

## Linked entities

- **Genes:** FOS (Fos proto-oncogene, AP-1 transcription factor subunit) [NCBI Gene 2353], JUN (Jun proto-oncogene, AP-1 transcription factor subunit) [NCBI Gene 3725], MMP1 (matrix metallopeptidase 1) [NCBI Gene 4312], MMP7 (matrix metallopeptidase 7) [NCBI Gene 4316], MMP8 (matrix metallopeptidase 8) [NCBI Gene 4317], MMP9 (matrix metallopeptidase 9) [NCBI Gene 4318]
- **Proteins:** FOS (Fos proto-oncogene, AP-1 transcription factor subunit)
- **Species:** Xenopus laevis (taxon 8355)

## Full-text entities

- **Genes:** fos.S (FBJ murine osteosarcoma viral oncogene homolog S homeolog) [NCBI Gene 447201] {aka c-fos, fos, xfos}, mapk1.S (mitogen-activated protein kinase 1 S homeolog) [NCBI Gene 398985] {aka erk, erk1, erk2, ert1, mapk, mapk1}, mmp8.S (matrix metallopeptidase 8 S homeolog) [NCBI Gene 495372] {aka mmp8}, actn1.L (actinin alpha 1 L homeolog) [NCBI Gene 399422] {aka a-actinin, actinin, actn1}, nfkb1.L (nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 L homeolog) [NCBI Gene 447632] {aka ebp-1, kbf1, nf-kappa-b, nf-kappaB, nfkb-p105, nfkb-p50}, mmp9.S (matrix metallopeptidase 9 gene 1 S homeolog) [NCBI Gene 379663] {aka MMP-9, clg4b, gelb, mandp2, mmp9, mmp9.1}, actl6a.S (actin like 6A S homeolog) [NCBI Gene 380143] {aka actin, actl6, actl6a, actl6a.L, arp4, arpn-beta}, mmp3.L (matrix metallopeptidase 3 L homeolog) [NCBI Gene 446898] {aka chds6, mmp-3, mmp13, mmp3, sl-1, stmy}, itgb1.L (integrin subunit beta 1 L homeolog) [NCBI Gene 397755] {aka cd29, fnrb, gpiia, itgb1, itgb1-a, itgb1-b}, fn1.S (fibronectin 1 S homeolog) [NCBI Gene 397744] {aka fibronectin, fn1}, pxn.S (paxillin S homeolog) [NCBI Gene 397826] {aka pxn}, mmp2.S (matrix metallopeptidase 2 S homeolog) [NCBI Gene 380389] {aka Xmmp2, clg4, clg4a, mmp-ii, mmp2, mona}, vcl.S (vinculin S homeolog) [NCBI Gene 373770] {aka vcl, vcl-A}, mmp1.S (matrix metallopeptidase 1 S homeolog) [NCBI Gene 495287] {aka col4, mmp1, mmp18}, jun.L (jun proto-oncogene L homeolog) [NCBI Gene 399400] {aka AP-1, c-Jun, jun}, atf3.L (activating transcription factor 3 L homeolog) [NCBI Gene 447311] {aka atf-3, atf3}, mmp8.L (matrix metallopeptidase 8 L homeolog) [NCBI Gene 380210] {aka mmp1}, mmp7.L (matrix metallopeptidase 7 L homeolog) [NCBI Gene 379369] {aka matrilysin, mmp-7, mmp7, pump-1}, junb.L (jun B proto-oncogene L homeolog) [NCBI Gene 432129] {aka junb}
- **Diseases:** infection (MESH:D007239), inflammation (MESH:D007249), scratch (MESH:D002372), haemostasis (MESH:D020141), myeloid (MESH:D007951), lupus erythematosus (MESH:D008180), bleeding (MESH:D006470), heart failure (MESH:D006333)
- **Chemicals:** MgSO4 (MESH:D008278), MO (MESH:D060172), Alexa Fluor 488 (MESH:C000711379), GM6001 (MESH:C078131), NaCl (MESH:D012965), S (MESH:D013455), methanol (MESH:D000432), NaHCO3 (MESH:D017693), Abcam (-), D609 (MESH:C046498), Batimastat (MESH:C080985), phalloidin (MESH:D010590), HEPES (MESH:D006531), zinc (MESH:D015032), Ficoll (MESH:D005362), MOs (MESH:D008982), CaCl2 (MESH:D002122), KCl (MESH:D011189), ROS (MESH:D017382), calcium (MESH:D002118), NO (MESH:D009569), paraformaldehyde (MESH:C003043)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Homo sapiens (human, species) [taxon 9606], Ambystoma mexicanum (axolotl, species) [taxon 8296], Danio rerio (leopard danio, species) [taxon 7955], Xenopus laevis (African clawed frog, species) [taxon 8355]

## Full text

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## Figures

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## References

52 references — full list in the complete paper: https://tomesphere.com/paper/PMC12917100/full.md

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Source: https://tomesphere.com/paper/PMC12917100