Proteomic analysis of Caenorhabditis elegans wound model reveals novel molecular players involved in repair

Wound repair is a multistep process which involves coordination of multiple molecular players from different cell types and pathways. Though the cellular processes that are taking place in order to repair damage is already known, molecular players involved in crucial pathways are still scarce. In this regard, the present study intends to uncover crucial players that are involved in the central repair events through proteomics approach which included 2-D GE and LC-MS/MS using Caenorhabditis elegans wound model. Initial gel-based 2-D GE and following protein-protein interaction (PPI) network analyses revealed active role of calcium signaling, acetylcholine transport and serotonergic neurotransmitter pathways. Further, gel-free LC-MS/MS and following PPI network analyses revealed the incidence of actin nucleation at the initial hours immediately after injury. Further by visualizing the PPI network and the interacting players, pink-1, a mitochondrial Serine/threonine-protein kinase which is known to regulate mitochondrial dynamics, was found to be the central player in facilitating the mitochondrial fission and its role was further verified using qPCR analysis and pink-1 transgenic worms. Overall, the study delivers new insights from crucial regulatory pathways and central players involved in wound repair using high throughput proteomic approaches and the mass spectrometry Data (PXD024629/PXD024744) are available via ProteomeXchange. Significance: Though, C. elegans is being explored as a wound model for more than a decade, global proteomic changes are not looked at yet upon injury and following repair. In this regard, the present study was carried out in C. elegans to uncover new insights from wound repair through global proteomic analysis. For this purpose, 2-D GE and LC-MS/MS analysis was carried out in unwounded and wounded samples and the PPI network constructed from the identified proteins included 2683 non redundant nodes which is actually 1/10th of the total nodes present in C. elegans whole PPI network available in the database as shown in the figure below. This is an added value of the present study which resulted with fruitful insights into crucial regulatory players and pathways that are regulated during wound repair.