.png){kind=icon}
.png){kind=icon}
Return
Mechanistic role for mTORC1 signaling in profibrotic toxicity of low-dose cadmium
.png){kind=icon}
PRE
AI
DOI：10.1016/j.taap.2024.117159.png)
.png){kind=icon}
Original request for help.png){kind=icon}
Share.png){kind=icon}
Save
Abstract
En 中文
Cadmium (Cd) is a toxic environmental metal that occurs naturally in food and drinking water. Cd is of increasing concern to human health due to its association with age-related diseases and long biological half-life. Previous studies show that low-dose Cd exposure via drinking water induces mechanistic target of rapamycin complex 1 (mTORC1) signaling in mice; however, the role of mTORC1 pathway in Cd-induced pro-fibrotic responses has not been established. In the present study, we used human lung fibroblasts to examine whether inhibiting the mTORC1 pathway prevents lung fibrosis signaling induced by low-dose Cd exposure. Results show that rapamycin, a pharmacological inhibitor of mTORC1, inhibited Cd-dependent phosphorylation of ribosomal protein S6, a downstream marker of mTORC1 activation. Rapamycin also decreased Cd-dependent increases in pro-fibrotic markers, alpha-smooth muscle actin, collagen 1 alpha 1 and fibronectin. Cd activated mitochondrial spare respiratory capacity in association with increased cell proliferation. Rapamycin decreased these responses, showing that mTORC1 signaling supports mitochondrial energy supply for cell proliferation, an important step in fibroblast trans-differentiation into myofibroblasts. Collectively, these results establish a key mechanistic role for mTORC1 activation in environmental Cd-dependent lung fibrosis.
Keywords:
Cadmium
Environmental exposure
Mitochondrial function
Mammalian target of rapamycin
Pulmonary fibrosis
Journal
IF:
3.4
Papers:
9.0K
Citations:
1.9W