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. 2022 Jun 27;11(13):2036.
doi: 10.3390/cells11132036.

Enoxaparin Increases D6 Receptor Expression and Restores Cytoskeleton Organization in Trophoblast Cells from Preeclampsia

Chiara Tersigni  1 , Giuseppe Maulucci  2   3 , Roberta Castellani  4 , Giada Bianchetti  2   3 , Marianna Onori  1 , Rita Franco  4 , Greta Barbaro  4 , Marco De Spirito  2   3 , Antonio Lanzone  1   4 , Giovanni Scambia  4   5 , Nicoletta Di Simone  6   7
Affiliations

Enoxaparin Increases D6 Receptor Expression and Restores Cytoskeleton Organization in Trophoblast Cells from Preeclampsia

Chiara Tersigni et al. Cells. .

Abstract

D6 is a scavenger receptor for CC chemokines expressed in the human placenta. It prevents excessive leukocyte tissue infiltration by internalizing chemokines through cytoskeleton-dependent intracellular transport. In preeclampsia (PE), the D6 receptor is overexpressed in trophoblast cells, but functionally impaired, due to cytoskeleton destructuring. Low molecular weight heparin (LMWH) represents a potential treatment for PE based on its anti-thrombotic and anti-inflammatory properties. Here, we investigated the effect of enoxaparin on D6 expression, and cytoskeleton organization primary cytotrophoblast cell cultures were obtained from the placentae of women with PE (n = 9) or uncomplicated pregnancy (n = 9). We demonstrated that enoxaparin is able to (i) increase D6 expression, and (ii) improve cytoskeletal fiber alignment in trophoblast cells from PE patients.

Keywords: D6; chemokines; cytoskeleton; heparin; placenta; preeclampsia.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
(A) Representative immunoblotting showing expression of D6 receptor in trophoblast cell lysates from PE or controls in basal conditions (0) and after incubation with LMWH for 24 h (1 and 10 UI/mL). (B) Quantitative analysis of Western blot results shows higher expression of D6 receptor in trophoblast cells from preeclamptic women (n = 3) after incubation with enoxaparin for 24 h (1 UI/mL) compared to basal conditions (0). No significant differences in terms of D6 expression were observed in trophoblast cells from normal pregnancy (CTR, n = 3) with or without LMWH treatment. (C–E) Confocal analysis of trophoblast cells showed a basal higher expression of D6 in preeclamptic women (n = 9) compared to controls (n = 9) and a significant increase of D6 expression in PE after cells incubation with LMWH (10 UI/mL) for 24 h. Data are expressed as the mean ± standard error (SE). PE: preeclampsia; CTR: control; LMWH: low molecular weight heparin; NS: not significant. * p < 0.05; **** p < 0.0001.
Figure 2
Figure 2
(A1–B2) F-actin staining of trophoblast cells from normal pregnant (A1,A2) and PE (B1,B2) women before (A1,B1) and after (A2,B2) LMWH incubation (10 UI/mL) for 24 h. (C) F-actin polymerization analyzed as eccentricity is significantly reduced in PE compared to controls. Incubation of trophoblast cells with LMWH significantly improved F-actin polymerization and cytoskeleton spatial organization. No significant difference was found in cells obtained from normal pregnant women after treatment with LMWH. Data are expressed as median with related confidence interval. ** p < 0.01.
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