The unique molecular targets associated antioxidant and antifibrotic activity of curcumin in in vitro model of acute lung injury: A proteomic approach

Bleomycin (BLM) injury is associated with the severity of acute lung injury (ALI) leading to fibrosis, a high-morbidity, and high-mortality respiratory disease of unknown etiology. BLM-induced ALI is marked by the activation of a potent fibrogenic cytokine transcription growth factor beta-1 (TGF beta-1), which is considered a critical cytokine in the progression of alveolar injury. Previously, our work demonstrated that a diet-derived compound curcumin (diferuloylmethane), represents its antioxidative and antifibrotic application in TGF-beta 1-mediated BLM-induced alveolar basal epithelial cells. However, curcumin-specific protein targets, as well as its mechanism using mass spectrometry-based proteomic approach, remain elusive. To elucidate the underlying mechanism, a quantitative proteomics approach and bioinformatics analysis were employed to identify the protein targets of curcumin in BLM or TGF-beta 1-treated cells. With subsequent in vitro experiments, curcumin-related pathways and cellular processes were predicted and validated. The current study discusses two separate proteomics experiments using BLM and TGF-beta 1-treated cells with the proteomics approach, various unique target proteins were identified, and proteomic analysis revealed that curcumin reversed the expressions of unique proteins like DNA topoisomerase 2-alpha (TOP2A), kinesin-like protein (KIF11), centromere protein F (CENPF), and so on BLM or TGF-beta 1 injury. For the first time, the current study reveals that curcumin restores TGF-beta 1 induced peroxisomes like PEX-13, PEX-14, PEX-19, and ACOX1. This was verified by subsequent in vitro assays. This study generated molecular evidence to deepen our understanding of the therapeutic role of curcumin at the proteomic level and may be useful to identify molecular targets for future drug discovery.

Automated summary

The study utilized a quantitative proteomics approach to identify protein targets of curcumin in BLM or TGF-beta 1-treated cells, revealing its effects on related pathways and cellular processes. It also discovered that curcumin can reverse the expression of specific proteins in lung injury.