Inhibition of Lysyl Oxidase by Cortisol Regeneration in Human Amnion: Implications for Rupture of Fetal Membranes

Zuo

et al. 2017

Sci Rep

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Serum amyloid A1 (SAA1) is an acute response protein, which is mainly produced by the liver, during infection. However, it remains unknown whether SAA1 can be produced in human fetal membranes where it is able to elicit events pertinent to labor initiation. We demonstrated that SAA1 was expressed in the fibroblasts and epithelium of the amnion and the trophoblasts of the chorion. Further study in human amnion fibroblasts showed that SAA1 production was augmented by interleukin-1β (IL-1β) and cortisol alone and synergistically, and SAA1 in turn induced the expression of IL-1β, interleukin-6 (IL-6), cyclooxygenase-2 (COX-2) and PGE2 production. These effects of SAA1 were mediated through activation of the NF-κB, p38 and ERK1/2 pathways via the toll-like receptor 4 (TLR4). Inhibition of TLR4 attenuated not only SAA1-induced activation of NF-κB, p38 and ERK1/2 but also increases in IL-1β, IL-6 and COX-2 expression. Moreover, SAA1 expression was increased in human amnion tissue following spontaneous labor. In conclusion, this study has demonstrated for the first time that SAA1 can be produced in human fetal membranes, which can be greatly induced in the presence of proinflammatory cytokines and glucocorticoids thereby producing effects associated with parturition.

Section: Discussionmentioning

confidence: 98%

Induction of pro-inflammatory genes by serum amyloid A1 in human amnion fibroblasts

Zuo

et al. 2017

Sci Rep

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“…As collagen IV is essential for the maintenance of epithelial basal membrane and in the assembling of other ECM structural proteins in the amnion (10,46,47), the induction of MMP7 expression by cortisol and the degradation of COL4A5 by MMP-7 are additional evidence of cortisol regeneration in ECM remodeling in the amnion, in addition to the autophagic and proteasomic degradation of collagen I and III (8,9) and inhibition of collagen crosslinking enzyme lysyl oxidase demonstrated previously (7). Of note, increased apoptosis of the amnion epithelial layer has been shown to be another contributor to membrane rupture (29,48).…”

Section: Discussionmentioning

confidence: 79%

“…These data suggest that the increase in MMP-7 abundance and decrease in CO-L4A5 abundance in the amnion tissue may be associated with the spontaneous rupture of membranes at parturition. Given that there is increased 11b-HSD1 abundance and cortisol regeneration in the amnion tissue at parturition (7) and the drastic induction of MMP7 expression by cortisol, it is likely that these reciprocal changes of MMP-7 and COL4A5 in the amnion tissue in spontaneous rupture of membranes at parturition are, at least in part, a result of the consequence of an increase of cortisol accumulation in the amnion.…”

Section: Role Of Ap-1 In the Induction Of Mmp-7 By Cortisolmentioning

confidence: 99%

“…The amnion is known to be the most tensile layer of the membranes because of its rich contents of collagens in the mesenchymal layer (4). Before membrane rupture, the extracellular matrix (ECM) in the mesenchymal layer of the amnion undergoes extensive remodeling, including collagen degradation and a loss in proteinprotein crosslinks (3,(5)(6)(7).…”

mentioning

confidence: 99%

“…Cortisol regenerated by 11b-HSD1 in the fetal membranes has been shown to induce a number of crucial events in human parturition (22), including stimulation of prostaglandin synthesis, inhibition of prostaglandin catabolism in the fetal membranes, and induction of estrogen synthesis in the placenta (23)(24)(25)(26). Recently, we revealed a novel role of cortisol regeneration in ECM remodeling in the amnion, including inhibition of lysyl oxidase, a collagen crosslinking enzyme (7), and degradation of collagen I and III via autophagic and proteosomic pathways (8,9). However, glucocorticoids, as a classical anti-inflammatory hormone, are believed to inhibit MMP expression in other parts of the body (27,28), which appears to be contradictory to the labor-initiating effects of cortisol in the fetal membranes.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Drastic induction of MMP‐7 by cortisol in the human amnion: implications for membrane rupture at parturition

et al. 2018

FASEB j.

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Preterm premature rupture of fetal membranes precedes 30–40% of preterm births. Activation of matrix metalloproteases (MMPs) is the one of the major causes of extracellular matrix (ECM) degradation in membrane rupture. Increased cortisol, regenerated by 11β‐hydroxysteroid dehydrogenase 1 in the amnion at parturition, is known to participate in a number of parturition‐pertinent events. However, whether cortisol has a role in the regulation of MMPs in the membranes is not known. Here, we addressed this issue using human amnion tissue, the most tensile layer of the membranes. RNA‐sequencing revealed that cortisol induced MMP7 expression dramatically in amnion fibroblasts, which was confirmed by real‐time quantitative RT‐PCR and Western blotting analysis in cortisol‐treated amnion explants and fibroblasts. Measurement of collagen IV α5 chain (COL4A5), a substrate for MMP‐7, showed that cortisol reduced its extracellular abundance, which was blocked by an antibody against MMP‐7. Moreover, increased MMP‐7 but decreased COL4A5 abundance was observed in the amnion tissue following labor‐initiated spontaneous rupture of membranes. Mechanistic studies showed that cortisol increased the phosphorylation of c‐Jun and the expression of c‐Fos, the 2 major components of activated protein 1 (AP‐1), respectively. The knocking down of c‐Fos or c‐Jun significantly attenuated the induction of MMP7 expression by cortisol. Chromatin immunoprecipitation assays showed that cortisol stimulated the enrichment of c‐Fos and c‐Jun at the AP‐1 binding site in the MMP7 promoter. The data suggest that induction of MMP7 by cortisol via AP‐1 may be a contributing factor to ECM degradation in membrane rupture at parturition.—Wang, L.‐Y., Wang, W.‐S., Wang, Y.‐W., Lu, J.‐W., Lu, Y., Zhang, C.‐Y., Li, W.‐J., Sun, K., Ying, H. Drastic induction of MMP‐7 by cortisol in the human amnion: implications for membrane rupture at parturition. FASEB J. 33, 2770–2781 (2019). http://www.fasebj.org

C/EBPδ drives key endocrine signals in the human amnion at parturition

Clinical & Translational Med

Zhou

et al. 2021

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Amnion‐derived prostaglandin E2 (PGE2) and cortisol are key to labor onset. Identification of a common transcription factor driving the expression of both cyclooxygenase‐2 (COX‐2) and 11β‐hydroxysteroid dehydrogenase 1 (11β‐HSD1), the key enzymes in their production, may hold the key to the treatment of pre‐term labor. Here, we have found that the CCAAT enhancer binding protein δ (C/EBPδ) is such a transcription factor which underlies the feed‐forward induction of COX‐2 and 11β‐HSD1 expression by their own products PGE2 and cortisol in human amnion fibroblasts so that their production would be ensured in the amnion for the onset of labor. Moreover, the abundance of C/EBPδ in the amnion increases along with COX‐2 and 11β‐HSD1 at term and further increases at parturition. Knockout of C/EBPδ in mice delays the onset of labor further supporting the concept. In conclusion, C/EBPδ pathway may be speculated to serve as a potential pharmaceutical target in the amnion for treatment of pre‐term labor.