The role and mechanism of FTO in pulmonary vessels.

Abstract

Pulmonary vascular remodeling (PVR) is the main factor of pulmonary hypertension (PH). The pathological characteristics of PVR are vascular smooth muscle hyperplasia, hypertrophy, and extensive damage. In vivo experiments, the expression of FTO in PH rat lung tissues of different rat models of hypoxia PH was observed by immunohistochemical method. mRNA microarray analysis was used to analyze the differential expressed genes in rat lung tissues. In vitro experiments, we developed models of overexpression and knockdown of FTO to study the effect of FTO protein expression on cell apoptotic, cell cycle, and the abundance of m⁶A. The expression of FTO was increased in PH rats. FTO knockdown can inhibit the proliferation of PASMCs, thereby regulating the cell cycle and reducing the expression of Cyclin D1 and the abundance of m⁶A, while overexpression of FTO leads to increased expression of Cyclin D1 and the abundance of m⁶A. FTO destroys the stability of Cyclin D1 by regulating the abundance of Cyclin D1 m⁶A, causing cell cycle arrest and inducing cell proliferation, thus inducing the occurrence and development of PVR in PH.