Inhibition of Bcl-2/xl With ABT-263 Selectively Kills Senescent Type II Pneumocytes and Reverses Persistent Pulmonary Fibrosis Induced by Ionizing Radiation in Mice.

ABSTRACT:

Purpose

Ionizing radiation (IR)-induced pulmonary fibrosis (PF) is an irreversible and severe late effect of thoracic radiation therapy. The goal of this study was to determine whether clearance of senescent cells with ABT-263, a senolytic drug that can selectively kill senescent cells, can reverse PF.

Methods and materials

C57BL/6J mice were exposed to a single dose of 17 Gy on the right side of the thorax. Sixteen weeks after IR, they were treated with 2 cycles of vehicle or ABT-263 (50 mg/kg per day for 5 days per cycle) by gavage. The effects of ABT-263 on IR-induced increases in senescent cells; elevation in the expression of selective inflammatory cytokines, matrix metalloproteinases, and tissue inhibitors of matrix metalloproteinases; and the severity of the tissue in

SUBMITTER: Pan J 

PROVIDER: S-EPMC6853175 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature