ArticlePediatric research2023
Elevated human placental heat shock protein 5 is associated with spontaneous preterm birth.
Article in Pediatric research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 8 citations in OpenAlex.
- Narrative Review on Therapies That Influence Inflammatory Responses During Extremely Premature Perinatal Respiratory Transition.Acta paediatrica (Oslo, Norway : 1992) · 2026Review
- Effect of non-optimal ambient temperature on preterm birth and its heterogeneity in various social sub-groups: a report from the Indo Gangetic Plains of India.BMC pregnancy and childbirth · 2026Article
- Multi-tissue miRNA networks in preterm birth: from molecular mechanisms to precision medicine.Frontiers in immunology · 2026Review
- Decoding the amniotic membrane transcriptome during equine ascending placentitis.Scientific reports · 2025Article
- VEGF-B is a novel mediator of ER stress which induces cardiac angiogenesis via RGD-binding integrins independent of VEGFR1/NRP activities.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- The endoplasmic reticulum protein HSPA5/BiP is essential for decidual transformation of human endometrial stromal cells.Scientific reports · 2024Article
- Preterm and Early-Term Delivery After Heat Waves in 50 US Metropolitan Areas.JAMA network open · 2024Article
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundSpecific heat shock proteins are associated with pregnancy complications, including spontaneous preterm birth (SPTB). Placental proteomics and whole exome sequencing recently suggested an association between heat shock protein HSPA5 and uncomplicated SPTB. In the present study, we investigated the localization of and possible roles for HSPA5 in SPTB.
methodsWestern blot was performed to validate the result from the previously published proteomic analysis. We used qPCR to assess mRNA expression of genes and immunohistochemistry and immunoelectron microscopy to examine localization of HSPA5 in placental tissue. We silenced the HSPA5 gene in the HTR8/SVneo human trophoblast cell line to investigate possible functions of HSPA5.
resultsHSPA5 was upregulated in placentas from SPTBs compared to spontaneous term births. We did not observe upregulation of HSPA5 mRNA in placental samples. The protein was localized in placental trophoblast in both spontaneous preterm and term placentas. Gene silencing of HSPA5 in human trophoblast cell culture affected the inflammatory response and decreased the expression of several proinflammatory genes.
conclusionsWe suggest that upregulation of HSPA5 in the placenta is associated with spontaneous preterm labor. HSPA5 may promote the inflammatory response and alter the anti-inflammatory state of the placenta which could eventually lead to premature labor. IMPACT: We validated upregulation of HSPA5 in placentas from spontaneous preterm birth. HSPA5 was not upregulated at transcriptional level which suggests that it may be regulated post-translationally. Silencing HSPA5 in a human trophoblast-derived cell line suggested that HSPA5 promotes expression of proinflammatory cytokines. The emerging inflammation could lead to spontaneous preterm labor. Identifying inflammatory pathways and factors associated with spontaneous preterm birth increases knowledge of the molecular mechanisms of premature labor. This could provide cues to predict imminent premature labor and lead to information about how to safely maintain pregnancies.
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