hsa_circ_0003218 Mitigates Trophoblast Dysfunction in Gestational Diabetes by Regulating TLR4/MyD88/NF-κB and NLRP3
Insights
This study reveals that hsa_circ_0003218 protects against gestational diabetes mellitus (GDM) by improving trophoblast function. It achieves this by inhibiting key inflammatory pathways, including TLR4/MyD88/NF-κB and NLRP3 inflammasomes.
Area of Science:
- Reproductive Biology
- Molecular Biology
- Endocrinology
Background:
- Gestational diabetes mellitus (GDM) is associated with trophoblast dysfunction.
- The specific molecular mechanisms underlying GDM-induced trophoblast dysfunction require further elucidation.
Purpose of the Study:
- To investigate the role and mechanism of hsa_circ_0003218 in trophoblast dysfunction in GDM.
- To determine if hsa_circ_0003218 can ameliorate GDM-related placental issues.
Main Methods:
- Quantified hsa_circ_0003218 expression in GDM and normal pregnancy serum and placental tissues using RT-qPCR.
- Assessed trophoblast proliferation, apoptosis, migration, and invasion in vitro under high glucose conditions.
- Analyzed inflammatory factors and key signaling pathway proteins (TLR4/MyD88/NF-κB, NLRP3 inflammasome) via ELISA and Western blot.
Main Results:
- hsa_circ_0003218 expression was significantly lower in GDM placentas and high glucose-treated trophoblasts.
- Overexpression of hsa_circ_0003218 reversed high glucose-induced impairments in trophoblast function (proliferation, migration, invasion, apoptosis).
- hsa_circ_0003218 suppressed the activation of the TLR4/MyD88/NF-κB cascade and NLRP3 inflammasomes.
Conclusions:
- hsa_circ_0003218 plays a protective role in GDM by maintaining trophoblast function.
- hsa_circ_0003218 exerts its protective effects by inhibiting the TLR4/MyD88/NF-κB signaling pathway and NLRP3 inflammasome activation.
Background:
This investigation sought to determine hsa_circ_0003218's role and mechanism in trophoblast dysfunction during gestational diabetes mellitus (GDM).
Methods:
The study involved forty pregnant women, comprising twenty with GDM and twenty with normal pregnancies. hsa_circ_0003218 expression levels in serum and placental tissues were detected by RT-qPCR. hTR8/ SVneo cells were exposed to high glucose (HG) in vitro and assayed for proliferation, apoptosis, migration, and invasion by CCK-8, flow cytometry, and Transwell tests, respectively. Inflammatory factors were detected by ELISA. TLR4/MyD88/NF-κB cascade and NLRP3 inflammasomes-associated proteins were detected by Western blot.
Results:
hsa_circ_0003218 was lowly expressed in placental tissues from GDM patients and HG-treated trophoblasts. hsa_circ_0003218 overexpression lessened HG-induced inhibition of trophoblast proliferation, migration, and invasion, and stimulation of apoptosis and inflammatory factor production. Furthermore, hsa_circ_0003218 prevented the activation of both the TLR4/MyD88/NF-κB cascade and the NLRP3 inflammasome.
Conclusions:
hsa_circ_0003218 improves trophoblast function in GDM by blocking the TLR4/MyD88/NF-κB cascade and preventing NLRP3 inflammasome activation.
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