Mapk13, also known as p38δ-MAPK, is a stress kinase that plays significant roles in various biological processes. It is involved in regulating epithelial stem cells, with potential implications in the structural remodeling that can occur after epithelial barrier injury. It may be part of pathways related to inflammation, mucus production, and cell growth control [2,4]. Genetic models, such as gene-knockout models, are valuable for studying its functions.

In Mapk13 gene-knockout mice, acute infectious illness is handled as expected, but these mice are protected against structural remodeling like basal-epithelial stem cell hyperplasia-metaplasia, immune activation, and mucinous differentiation after respiratory viral injury. In corresponding cell models, Mapk13-deficiency directly attenuates basal-ESC growth and organoid formation. In human studies, marked induction/activation of basal-cell MAPK13 is seen in asthma and COPD samples, and MAPK13 gene-knockdown inhibits human basal-ESC growth in culture. This shows that Mapk13 controls structural remodeling and disease after epithelial injury [2]. Additionally, a potent MAPK13-14 inhibitor (NuP-3) can prevent respiratory airway inflammation and mucus production in minipig models of airway disease, indicating its role in these respiratory conditions [1,3].

In conclusion, Mapk13 is crucial in regulating epithelial stem cells and subsequent structural remodeling processes. The gene-knockout mouse models have revealed its significance in post-epithelial-injury disease development, especially in respiratory diseases like asthma and COPD. Understanding Mapk13's functions provides potential therapeutic targets for treating these and related conditions.

References:

1. Keeler, Shamus P, Wu, Kangyun, Zhang, Yong, Romero, Arthur G, Holtzman, Michael J. 2023. A potent MAPK13-14 inhibitor prevents airway inflammation and mucus production. In American journal of physiology. Lung cellular and molecular physiology, 325, L726-L740. doi:10.1152/ajplung.00183.2023. https://pubmed.ncbi.nlm.nih.gov/37847710/

2. Wu, Kangyun, Zhang, Yong, Mao, Dailing, Romero, Arthur G, Holtzman, Michael J. 2024. MAPK13 controls structural remodeling and disease after epithelial injury. In bioRxiv : the preprint server for biology, , . doi:10.1101/2024.05.31.596863. https://pubmed.ncbi.nlm.nih.gov/38895360/

3. Keeler, Shamus P, Wu, Kangyun, Zhang, Yong, Romero, Arthur G, Holtzman, Michael J. 2023. A potent MAPK13-14 inhibitor prevents airway inflammation and mucus production. In bioRxiv : the preprint server for biology, , . doi:10.1101/2023.05.26.542451. https://pubmed.ncbi.nlm.nih.gov/37292761/

4. Zhang, Yong, Wu, Kangyun, Mao, Dailing, Romero, Arthur G, Holtzman, Michael J. 2024. A first-in-kind MAPK13 inhibitor that can correct stem cell reprogramming and post-injury disease. In bioRxiv : the preprint server for biology, , . doi:10.1101/2024.08.21.608990. https://pubmed.ncbi.nlm.nih.gov/39229202/