Discover of a novel player in human skin wound healing

Researchers at Karolinska Institutet have identified a novel RNA molecular named ‘WAKMAR1’, that can help keratinocyte migrate, a pivotal step to recover the skin barrier upon injury. In patients with hard-to-heal wounds, WAKMAR1 is lacking. The study is published in the scientific journal PNAS, Proceedings of the National Academy of Sciences.

The ability to repair damaged tissue and heal wounds is a fundamental and crucial biological process. If the wound healing does not work, this results in chronic wounds. This is a common medical problem in old and overweight people, as well as in patients who have diabetes, reduced blood circulation or spinal cord injury. What molecular mechanisms contribute to the emergence of chronic wounds are mostly unknown, which hampers the development of more effective treatment.

First line of evidence demonstrating that lncRNAs play an essential role in human skin wound healing

Constituting the majority of the transcriptional output of the human genome, the functional importance of long non-coding (lncRNAs) has only recently been recognized. Their role in skin wound healing is virtually unknown. Now researchers at Karolinska Institutet have found a skin specific lncRNA, which they named as Wound and Keratinocyte Migration Associated lncRNA 1 (WAKMAR1) and plays an important role in human skin wound healing. WAKMAR1 was found to regulate a network of genes critical for cell migration, most of which were under the control of a key transcription factor E2F1. Most important, the researchers discovered that WAKMAR1 expression was increased during physiologic wound healing, while in human non-healing wounds, its level was significantly lower compared to normal wounds under re-epithelization. This study provides the first line of evidence demonstrating that lncRNAs play an essential role in human skin wound healing. Further exploration of the epigenetic regulatory network will open exciting opportunities for developing more effective wound therapy.

The research was supported through funding from the Hedlunds Foundation, Jeanssons Foundation, Lars Hiertas Foundation, Margaretha af Ugglas Foundation, Ming Wai Lau Centre for Reparative Medicine, National Natural Science Foundation of China, Ragnar Söderbergs Foundation, Swedish Research Council, Swedish Psoriasis Foundation, Tore Nilsons Foundation, Welander and Finsens Foundation, Åke Wibergs Foundation, and Karolinska Institutet.

Publication

”Human skin long noncoding RNA WAKMAR1 regulates wound healing by enhancing keratinocyte migration” Dongqing Li, Lara Kular, Manika Vij, Eva K. Herter, Xi Li, Aoxue Wang, Tongbin Chu, Maria-Alexandra Toma, Letian Zhang, Eleni Liapi, Ana Mota, Lennart Blomqvist, Irène Gallais Sérézal, Ola Rollman, Jakob D. Wikstrom, Magda Bienko, David Berglund, Mona Ståhle, Pehr Sommar, Maja Jagodic, and Ning Xu Landén

PNAS, online 24 April 2019, https://doi.org/10.1073/pnas.1814097116