PMID- 34295778 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220425 IS - 2224-4344 (Print) IS - 2224-4344 (Electronic) IS - 2224-4336 (Linking) VI - 10 IP - 6 DP - 2021 Jun TI - Effect of SOCS3 on apoptosis of human trophoblasts via adjustment of the JAK2/STAT3 signaling pathway in preterm birth. PG - 1637-1646 LID - 10.21037/tp-21-39 [doi] AB - BACKGROUND: The expression of suppressor of cytokine signaling 3 (SOCS3) was induced by interleukin-6 (IL-6) in preterm placental tissues. However, its role in IL-6 induced apoptosis of trophoblast cells derived from preterm placental tissues remains to be elucidated. METHODS: Primary cytotrophoblasts from human preterm placental tissues were used to stably knock down and overexpress the level of SOCS3 by corresponding lentiviral vectors and the expression of SOCS3 was validated by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot. The effect of SOCS3 overexpression or knockdown on the proliferation and apoptosis of IL-6 treated human cytotrophoblasts were determined by Cell Counting Kit-8 (CCK8) assay and Annexin-V/Propidium Iodide (PI) double-staining assay, respectively. Based on it, we detected the proteins associated with the Janus Tyrosine Kinase (JAK)/Signal Transducer and Activator of Transcription (STAT) pathway and apoptosis, such as JAK2, p-JAK2, STAT3, p-STAT3, B-cell lymphoma-2 (Bcl-2) and BCL2-associated X (Bax) by Western blot. RESULTS: IL-6-treatment resulted in significant apoptosis of human cytotrophoblasts. Overexpressing SOCS3 in the cytotrophoblasts reduced cell apoptosis, while the knockdown of SCOS3 had the opposite effects. Further analyses showed that SOCS3 overexpression inhibited JAK2 and STAT3 phosphorylation, which was induced by IL-6 stimulation. CONCLUSIONS: SOCS3 plays a protective role in human preterm placental tissue-derived cytotrophoblasts from IL-6 induced apoptosis by feedback inhibition of JAK2/STAT3 signaling. CI - 2021 Translational Pediatrics. All rights reserved. FAU - Yin, Yin AU - Yin Y AD - Department of Obstetrics and Gynecology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China. FAU - Qu, Lin AU - Qu L AD - Department of Obstetrics and Gynecology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China. FAU - Zhu, Dicong AU - Zhu D AD - State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China. FAU - Wu, Yang AU - Wu Y AD - Department of Obstetrics and Gynecology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China. FAU - Zhou, Xin AU - Zhou X AD - Department of Obstetrics and Gynecology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China. LA - eng PT - Journal Article PL - China TA - Transl Pediatr JT - Translational pediatrics JID - 101649179 PMC - PMC8261589 OTO - NOTNLM OT - JAK2/STAT3 signaling OT - Preterm birth OT - apoptosis OT - interleukin-6 (IL-6) OT - suppressor of cytokine signaling 3 (SOCS3) COIS- Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/tp-21-39). The authors have no conflicts of interest to declare. EDAT- 2021/07/24 06:00 MHDA- 2021/07/24 06:01 PMCR- 2021/06/01 CRDT- 2021/07/23 06:51 PHST- 2021/01/29 00:00 [received] PHST- 2021/05/12 00:00 [accepted] PHST- 2021/07/23 06:51 [entrez] PHST- 2021/07/24 06:00 [pubmed] PHST- 2021/07/24 06:01 [medline] PHST- 2021/06/01 00:00 [pmc-release] AID - tp-10-06-1637 [pii] AID - 10.21037/tp-21-39 [doi] PST - ppublish SO - Transl Pediatr. 2021 Jun;10(6):1637-1646. doi: 10.21037/tp-21-39.