Potential Therapeutic Targets for Leishmaniasis: Modulating Cytokine Production and ECM Organization

Abstract

Cutaneous leishmaniasis (CL) is a parasitic disease that causes skin ulcers, which often receive inadequate treatment. The pathophysiological mechanisms underlying these wounds are complex and not well understood. In this study, we performed co-expression network analyses on RNAseq data from skin biopsies of CL and healthy samples and identified 6,096 differentially expressed genes, with 456 proposed causative biomarkers of skin ulcers in CL. We grouped these genes based on functional analysis into three important operational groups related to wound healing. Our results suggest that the genes responsible for producing tissue-damaging cytokines play a significant role in tissue damage and wound healing prevention. Additionally, we identified changes in the expression of genes involved in extracellular matrix (ECM) organization and matrix metalloproteinase (MMP) activity, which can disrupt ECM activity and fail to heal the wounds. Targeting these genes involved in ECM organization and MMP activity could potentially help to restore normal tissue repair processes and reduce tissue damage during Leishmania infection. However, further research is needed to fully understand the roles of these genes in the disease and their potential as therapeutic targets. The results of this study provide valuable insights into the underlying pathophysiological mechanisms of CL-induced skin ulcers and can help develop better treatment strategies.