Pulmonary artery smooth muscle cell HIF-1 α regulates endothelin expression via microRNA-543.

Pulmonary artery smooth muscle cell HIF-1α regulates endothelin expression via microRNA-543. Am J Physiol Lung Cell Mol Physiol. 2018 May 10;: Authors: Wang CC, Ying L, Barnes EA, Adams ES, Kim FY, Engel KW, Alvira CM, Cornfield DN Abstract Pulmonary artery smooth muscle cells (PASMC) express endothelin (ET-1) which modulates the pulmonary vascular response to hypoxia. Although cross-talk between hypoxia-inducible factor-1α (HIF-1α), an O2-sensitive transcription factor, and ET-1 is established, the cell-specific relationship between HIF-1α and ET-1 expression remains incompletely understood. We tested the hypotheses that in PASMC: (i) HIF-1α expression constrains ET-1 expression; and (ii) a specific microRNA (miRNA) links HIF-1α and ET-1 expression. In human PASMC (hPASMC), depletion of HIF-1α with siRNA, increased ET-1 expression at both the mRNA and protein level (p<0.01). In HIF-1α-/- murine (m)PASMC, ET-1 gene and protein expression was increased (p<0.0001) compared to HIF-1α+/+ cells. miRNA profiles were screened in hPASMC transfected with siRNA-HIF-1α and RNA hybridization performed on the Agilent human miRNA microarray. With HIF-1α depletion, miRNA-543 increased by 2.4 fold (p<0.01). In hPASMC, miRNA-543 overexpression increased ET-1 gene (p<0.01) and protein (p<0.01) expression, decreased TWIST gene expression (p<0.05) and increased ET-1 gene and protein expression, compared to NTC (p<0.01). M...
Source: Am J Physiol Lung Ce... - Category: Respiratory Medicine Authors: Tags: Am J Physiol Lung Cell Mol Physiol Source Type: research