Unveiling Molecular Signatures: Gene Expression Analysis in Induced Fibrotic Models

Fibrosis is a pathological process affecting millions worldwide, arising from diverse causes such as impaired wound healing, viral infections, or toxin exposure. In severe cases, fibrosis leads to tissue dysfunction and, in organs like the liver, may progress to cirrhosis, significantly reducing overall physiological function. While fibrosis shares key mechanisms with wound healing, it is characterized by dysregulated repair processes, excessive extracellular matrix (ECM) deposition, and the formation of nonfunctional tissue. In most organs, fibrosis is irre-versible; however, the liver possesses a remarkable regenerative capacity, allowing functional recovery even after substantial tissue loss.
This thesis aimed to gain a deeper understanding of fibrosis and wound healing regulation across different organs to identify both shared and organ-specific mechanisms. To achieve this, we analyzed two pulmonary fibrosis models (Bleomycin and Pantoea agglomerans) and one hepatic fibrosis models (CCl₄-induced fibrosis). Additionally, we investigated wound heal-ing processes using a partial hepatectomy (PH) model for liver regeneration and a skin wound healing model in mice. Samples were collected at multiple time points to assess regenerative potential and track molecular changes over time. Single-channel microarray analysis was per-formed, and data were analyzed using the Bioconductor packages in R Studio.
Across all models, we observed common activation of inflammatory responses, DNA repair and replication, and cell cycle checkpoint pathways, suggesting a conserved regenerative at-tempt. However, organ-specific differences emerged. In the lung models, cholesterol biosyn-thesis exhibited opposing activity patterns, while iron accumulation was linked to progressive fibrosis. In the liver, toxin-induced fibrosis (CCl₄) was associated with lipoprotein pathway ac-tivation, whereas surgical liver damage (PH) predominantly triggered DNA repair and prolifer-ation, supporting regeneration over fibrosis. The skin model revealed age-dependent differ-ences, with older mice exhibiting increased activation of DNA repair, proliferation, and struc-tural protein binding pathways, while young mice showed reduced collagen biosynthesis and oxidative stress response.
Our findings provide insights into fibrosis and wound healing regulation, emphasizing both shared and tissue-specific responses. The identification of potential compensatory mecha-nisms, such as Wnt signaling downregulation and iron-associated fibrosis, highlights promising areas for future research. Understanding these molecular patterns may contribute to the development of targeted therapies that promote regeneration while mitigating pathological fibrosis.