[No authors listed]
Hypoxia serves a critical role in the pathogenesis of liver fibrosis. Hypoxiaâinducible factor 1α (HIF1âα) is induced when cells are exposed to low O2 concentrations. Recently, it has been suggested that Rhoâassociated coiledâcoilâforming kinase 1 (ROCK1) may be an important HIF1âα regulator. In the present study, it was analyzed whether crosstalk between HIF1âα and ROCK1 regulates cell proliferation and collagen synthesis in hepatic stellate cells (HSCs) under hypoxic conditions. For this purpose, a rat hepatic HSC line (HSCâT6) was cultured under hypoxic or normoxic conditions, and HIF1âα and ROCK1 expression was measured at different time points. Additionally, HSCâT6 cells were transfected with HIF1âα small interfering RNA (siHIF1âα), and measured protein expression and mRNA transcript levels of αâsmooth muscle actin, collagen 1A1 and ROCK1. Collagen 3A1 secretion was also measured by ELISA. Cell proliferation was assessed by the MTT assay under these hypoxic conditions. The results indicated that a specific ROCK inhibitor, Yâ27632, increased HIF1âα and ROCK1 expression over time in HSCâT6 cells in response to hypoxia. In addition, knockdown of HIF1âα inhibited HSCâT6 proliferation, suppressed collagen 1A1 expression, decreased collagen 3A1 secretion and attenuated ROCK1 expression. Notably, ROCK1 inhibition caused HSCâT6 quiescence, suppressed collagen secretion and downregulated HIF1âα expression. Collectively, these findings indicated that the interplay between HIF1âα and ROCK1 may be a critical factor that regulates cell proliferation and collagen synthesis in rat HSCs under hypoxia.
KEYWORDS: {{ getKeywords(articleDetailText.words) }}
Sample name | Organism | Experiment title | Sample type | Library instrument | Attributes | |||||||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
{{attr}} | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
{{ dataList.sampleTitle }} | {{ dataList.organism }} | {{ dataList.expermentTitle }} | {{ dataList.sampleType }} | {{ dataList.libraryInstrument }} | {{ showAttributeName(index,attr,dataList.attributes) }} |
{{ list.authorName }} {{ list.authorName }} |