HMGB1 is mechanistically essential in the development of experimental pulmonary hypertension.

HMGB1 is mechanistically essential in the development of experimental pulmonary hypertension. Am J Physiol Cell Physiol. 2018 Dec 05;: Authors: Dai M, Xiao R, Cai L, Ge T, Zhu L, Hu Q Abstract Pulmonary hypertension (PH) is a mortal disease featured with pulmonary vascular constriction and remodeling, right heart failure and eventual death. Several reports showed that high mobility group box 1 (HMGB1) appears to be critical for the development of PH, the underlying mechanism, however has not been revealed. Experiments from the current study demonstrated that the HMGB1 level was elevated in the lung tissue and blood plasma of rats after chronic hypoxia exposure and monocrotaline treatment. The HMGB1 was originally located within nucleus and translocated to cytoplasm of pulmonary artery smooth muscle cells (PASMCs) upon hypoxia exposure, a process that appeared mediated by endogenous H2O2. The exposure of HMGB1 mobilized calcium signaling in PASMCs, a response which was attenuated by extracellular Ca2+ removal, toll-like receptor 4 (TLR4) inhibition by TAK-242, or transient receptor potential channel (TRPC) suppression with 2-APB and SKF-96365. The sustained phosphorylation of Akt pathway modulated HMGB1-induced migration of PASMCs. The blockage of HMGB1 with glycyrrhizin, anti-HMGB1 neutralizing antibody attenuated lung inflammation and PH establishment in rats after hypoxia exposure and monocrotaline treatment. The above findings rev...
Source: Am J Physiol Cell Ph... - Category: Cytology Authors: Tags: Am J Physiol Cell Physiol Source Type: research