PRR34‐AS1 overexpression promotes protection of propofol pretreatment against ischemia/reperfusion injury in a mouse model after total knee arthroplasty via blockade of the JAK1‐dependent JAK‐STAT signaling pathway. Issue 3 (25th September 2019)

• Record Type: Journal Article
• Authors: Fang, Hua; Zhang, Fang‐Xiang; Li, Hua‐Feng; Yang, Miao; Liao, Ren; Wang, Ru‐Rong; Wang, Quan‐Yun; Zheng, Peng‐Cheng; Zhang, Jian‐Ping
• Is Part Of: Journal of cellular physiology. Volume 235:Issue 3(2020:Mar.)
• Page Start: 2545
• Page End: 2556
• Publication Date: 2019-09-25
• Subjects: apoptosis -- ischemia/reperfusion injury -- JAK1 -- JAK‐STAT signaling pathway -- proliferation -- propofol -- PRR34‐AS1 -- total knee arthroplasty; Physiology -- Periodicals; Cell physiology -- Periodicals; 571.6
• DOI: 10.1002/jcp.29158
• Languages: English
• ISSNs: 0021-9541

Abstract

Abstract: Long noncoding RNAs have been documented to be protective against ischemia/reperfusion (I/R) injury. However, few research works have focused on the protective effects of PRR34‐AS1 on I/R injury after total knee arthroplasty (TKA). The objective of the present study was to investigate the possible effect of PRR34‐AS1 on I/R injury after TKA. A mouse model with I/R injury after TKA was established. The interaction between PRR34‐AS1 and Janus kinase 1 (JAK1) was examined and thoroughly investigated. Next, the effects of PRR34‐AS1 on the expression of apoptosis‐related proteins, JAS‐signal transducer and activator of transcription (STAT) signaling pathways, and inflammation‐related genes, chondrocyte proliferation, and apoptosis were analyzed after gain‐ and loss‐of‐function experiments. Attenuated symptoms were observed in mice pretreated with propofol, which was evidenced by decreased positive expression rate of JAK1 protein and superoxide dismutase content along with increased malondialdehyde content and IL‐10 levels. PRR34‐AS1 was poorly expressed in mice with I/R injury after TKA. JAK1 was a target of PRR34‐AS1. Upregulated PRR34‐AS1 diminished expression of JAK1, STAT1, JAK2, and STAT3 as well as cell apoptosis, while enhancing cell proliferation in vitro. Furthermore, JAK1 silencing could reverse the suppressed cell proliferation and enhanced cell apoptosis of chondrocytes imposed by silencing PRR34‐AS1. Upregulation of PRR34‐AS1 can potentially relieve I/R injury after TKA in mice pretreated with propofol through inhibition of the JAS‐STAT signaling pathway by targeting JAK1.