The protective effect of leukemia inhibitory factor on apoptosis of BMSCs induced by hypoxia and serum-deprivation

Wang, Xiaoqi1,2,3; Huang, Jing2,3; Ou, Yanjing2,3,4,5,6; Zhang, Shuang2,3; Fan, Le7; Liang, Youde8; Wang, Yining2,3; Zhou, Yi2,3,9,10

2023

AMERICAN JOURNAL OF TRANSLATIONAL RESEARCH   Impact Factor & Quartile

1943-8141

Objectives: Bone marrow-derived mesenchymal stem cells (BMSCs) -based tissue engineering is an important strategy for treatment of bone defects. However, the ischemia environment limits the survival and biological functions of BMSCs. The present study aimed to investigate the effect of leukemia inhibitory factor (LIF) on the apoptosis of BMSCs induced by hypoxia and serum-deprivation (H & SD) as well as the underlying pathway mechanism. Methods: Mitochondrial membrane potential (MMP) was determined by flow cytometry. The apoptotic phenomenon of nuclear morphology was detected by fluorescence microscope. The ratio of apoptotic BMSCs was investigated by Annexin V/propidium iodide (PI) double staining and flow cytometric analysis. The expression of apoptosis-related molecules was detected by quantitative polymerase chain reaction (qPCR) and western blotting. Results: H & SD treatment induced a series of apoptotic phenotypes, including the downregulation of MMP, the apoptotic phenomenon of nuclear morphology, the increased rate of BMSCs at early and late apoptotic stage, and the reduced B-cell lymphoma-2 (Bcl-2)/Bcl-2-associated X (Bax) ratio. Administration of recombinant LIF alleviated the apoptosis of BMSCs induced by H & SD, which was reflected in recovery of MMP, morphology of nuclei, rate of apoptotic cells and inhibition of cleaved Caspase-3. The results of western blot demonstrated that phosphorylation of janus kinase (JAK) 1 and signal transducer and activator of transcription (STAT) 3 was inhibited by H & SD treatment, which was upregulated by LIF administration. JAK1-specific inhibitor GLPG0634 or STAT3-specific inhibitor S3I-201 eliminated the protective effects of LIF on the apoptosis of BMSCs. Conclusion: These data indicated that LIF played a protective role in apoptosis of BMSCs induced by ischemia via activating JAK1/STAT3 signaling pathway.

BMSCs LIF hypoxia serum-deprivation apoptosis JAK1/STAT3

SCI

English

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National Natural Science Foundation of China["82071090","82001014","82201057"] ; China Postdoc-toral Science Foundation[295589] ; OpenResearch Fund Program of Hubei-MOST KLOS amp; KLOBM[202203] ; Hubei Provincial Natural Science Foundation Innovation and Development Joint Fund[2022CFD005]

Oncology ; Research & Experimental Medicine

Oncology ; Medicine, Research & Experimental

WOS:001032073000006

E-CENTURY PUBLISHING CORP

Web of Science

1.Soochow Univ, Dept Stomatol, Affiliated Hosp 1, Suzhou, Jiangsu, Peoples R China
2.Wuhan Univ, State Key Lab Breeding Base Basic Sci Stomatol Hub, Wuhan, Hubei, Peoples R China
3.Wuhan Univ, Sch & Hosp Stomatol, Minist Educ, Key Lab Oral Biomed, Wuhan, Hubei, Peoples R China
4.Fujian Med Univ, Fujian Key Lab Oral Dis, Fuzhou, Fujian, Peoples R China
5.Fujian Med Univ, Sch & Hosp Stomatol, Fujian Coll & Univ, Fujian Prov Engn Res Ctr Oral Biomat, Fuzhou, Fujian, Peoples R China
6.University, Fujian Med Univ, Sch & Hosp Stomatol, Stomatol Key Lab,Fujian Coll & Univ, Fuzhou, Fujian, Peoples R China
7.Sun Yat sen Univ, Hosp Stomatol, Guanghua Sch Stomatol, Dept Prosthodont,Guangdong Prov Key Lab Stomatol, Guangzhou, Guangdong, Peoples R China
8.Southern Univ Sci & Technol, Yantian Hosp, Shenzhen, Guangdong, Peoples R China
9.Wuhan Univ, State Key Lab Breeding Base Basic Sci Stomatol Hub, 237 Luoyu Rd, Wuhan 430079, Hubei, Peoples R China
10.Wuhan Univ, Sch & Hosp Stomatol, Minist Educ, Key Lab Oral Biomed, 237 Luoyu Rd, Wuhan 430079, Hubei, Peoples R China

Wang, Xiaoqi,Huang, Jing,Ou, Yanjing,et al. The protective effect of leukemia inhibitory factor on apoptosis of BMSCs induced by hypoxia and serum-deprivation[J]. AMERICAN JOURNAL OF TRANSLATIONAL RESEARCH,2023,15(6).

Wang, Xiaoqi.,Huang, Jing.,Ou, Yanjing.,Zhang, Shuang.,Fan, Le.,...&Zhou, Yi.(2023).The protective effect of leukemia inhibitory factor on apoptosis of BMSCs induced by hypoxia and serum-deprivation.AMERICAN JOURNAL OF TRANSLATIONAL RESEARCH,15(6).

Wang, Xiaoqi,et al."The protective effect of leukemia inhibitory factor on apoptosis of BMSCs induced by hypoxia and serum-deprivation".AMERICAN JOURNAL OF TRANSLATIONAL RESEARCH 15.6(2023).