FAM172A supervises ER (endoplasmic reticulum) stress-triggered autophagy in the epidural fibrosis process.

Abstract

Lumbar laminectomy is usually utilized for lumbar disc herniation (LDH), but also causes epidural fibrosis (EF) process associated with abnormal proliferation of fibroblasts. FAM172A is associated with ER stress and cell proliferation, but its mechanism was unclear, especially in the process of EF. Therefore, the regulation of FAM172A on the calcium flux and autophagy in fibroblasts were investigated by inducing ER stress with tunicamycin and upexpression or downexpression of FAM172A. The calcium flux was determined using Fluo-3, and autophagy was examined with immunofluorescence or western blot for LC3, Beclin-1, ATG-5, and p62. Moreover, the apoptotic protein of Bax and Bcl-2 was detected, too. Furthermore, the laminectomy model was constructed and then dealt with overexpression of FAM172A. Tunicamycin-induced endoplasmic reticulum (ER) stress and autophagy process in fibroblasts were associated with the calcium flux regulated by FAM172A, especially in EF cells. Besides, tunicamycin induced autophagy and suppressed cell apoptosis of fibroblasts. Furthermore, FAM72A repressed the proliferation of fibroblasts and the process of EF in the laminectomy model through the mediation of the autophagy process. Tunicamycin-induced endoplasmic reticulum (ER) stress in fibroblasts was associated with calcium flux mediated by FAM172A. FAM72A participated in the autophagy regulation of fibroblasts and maybe the key interaction regulator of apoptosis and autophagy in fibroblasts, especially for epidural scar cells.