PMID- 32383265 OWN - NLM STAT- MEDLINE DCOM- 20210405 LR - 20211204 IS - 1097-4652 (Electronic) IS - 0021-9541 (Linking) VI - 235 IP - 12 DP - 2020 Dec TI - NLRC3 inhibits PDGF-induced PASMCs proliferation via PI3K-mTOR pathway. PG - 9557-9567 LID - 10.1002/jcp.29763 [doi] AB - Few studies about nucleotide-oligomerization domain-like receptor subfamily C3 (NLRC3) in PASMCs have been conducted. This research aimed to investigate the role of NLRC3 on platelet-derived growth factor (PDGF)-induced proliferation of pulmonary artery smooth muscle cells (PASMCs) and its underlying mechanism. We found that the proliferation of PASMCs stimulated with PDGF decreased when phosphoinositide 3-kinase (PI3K) or mammalian target of rapamycin (mTOR) inhibitors pretreatment. Overexpression of NLRC3 inhibited the proliferation of PASMCs and the phosphorylation of PI3K and mTOR while knocking down NLRC3 reversed this effect. Targeted to PI3K or mTOR can also reverse the effect of NLRC3. Activation of PI3K increased the phosphorylation of mTOR while inhibition of PI3K reduced it. Our data suggest that PDGF can induce abnormal proliferation of PASMCs, and NLRC3 suppresses activation of the PI3K-mTOR signaling thus inhibits PASMCs proliferation. These findings unveiled the effect of NLRC3 as an inhibitor of the PI3K-mTOR pathway mediating protection against PASMCs proliferation. CI - (c) 2020 Wiley Periodicals LLC. FAU - Zha, Li-Huang AU - Zha LH AUID- ORCID: 0000-0002-8024-4501 AD - Department of Cardiology, Xiangya Hospital, Central South University, Changsha, Hunan, China. FAU - Zhou, Jun AU - Zhou J AD - Department of Medical Science Research Center, Xiangya Hospital, Central South University, Changsha, Hunan, China. FAU - Tan, Yilong AU - Tan Y AD - Department of Ultrasonography, Zhuzhou Hospital, Central South University, Zhuzhou, Hunan, China. FAU - Guo, Shuhong AU - Guo S AD - Department of Cardiology, Zhuzhou Hospital, Central South University, Zhuzhou, Hunan, China. FAU - Zhang, Men-Qiu AU - Zhang MQ AD - Department of Cardiology, Xiangya Hospital, Central South University, Changsha, Hunan, China. FAU - Li, Sheng AU - Li S AD - Department of Cardiology, Xiangya Hospital, Central South University, Changsha, Hunan, China. FAU - Yan, Peng AU - Yan P AD - Department of Cardiology, Xiangya Hospital, Central South University, Changsha, Hunan, China. FAU - Yu, Zai-Xin AU - Yu ZX AUID- ORCID: 0000-0002-3555-1887 AD - Department of Cardiology, Xiangya Hospital, Central South University, Changsha, Hunan, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200507 PL - United States TA - J Cell Physiol JT - Journal of cellular physiology JID - 0050222 RN - 0 (Intercellular Signaling Peptides and Proteins) RN - 0 (NLRC3 protein, human) RN - 0 (Phosphoinositide-3 Kinase Inhibitors) RN - 0 (Platelet-Derived Growth Factor) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) SB - IM MH - Animals MH - Cell Proliferation/genetics MH - Gene Expression Regulation/drug effects MH - Gene Knockdown Techniques MH - Humans MH - Intercellular Signaling Peptides and Proteins/*genetics MH - Myocytes, Smooth Muscle/metabolism MH - Phosphatidylinositol 3-Kinases/*genetics/pharmacology MH - Phosphoinositide-3 Kinase Inhibitors/*pharmacology MH - Phosphorylation/drug effects MH - Platelet-Derived Growth Factor/pharmacology MH - Pulmonary Artery/growth & development/metabolism/pathology MH - Rats MH - TOR Serine-Threonine Kinases/antagonists & inhibitors/*genetics OTO - NOTNLM OT - NLRC3 OT - PASMCs OT - PI3K OT - mTOR OT - proliferation EDAT- 2020/05/10 06:00 MHDA- 2021/04/07 06:00 CRDT- 2020/05/09 06:00 PHST- 2019/07/09 00:00 [received] PHST- 2020/04/23 00:00 [accepted] PHST- 2020/05/10 06:00 [pubmed] PHST- 2021/04/07 06:00 [medline] PHST- 2020/05/09 06:00 [entrez] AID - 10.1002/jcp.29763 [doi] PST - ppublish SO - J Cell Physiol. 2020 Dec;235(12):9557-9567. doi: 10.1002/jcp.29763. Epub 2020 May 7.