Roles and mechanisms of TRPC3 and the PLCγ/PKC/CPI-17 signaling pathway in regulating parturition Corrigendum in /10.3892/mmr.2018.8572

Chen,Jing; Zheng,Dongming; Cui,Hong; Liu,Sishi; Zhang,Lijuan; Liu,Caixia

doi:10.3892/mmr.2017.7998

Roles and mechanisms of TRPC3 and the PLCγ/PKC/CPI-17 signaling pathway in regulating parturition

Corrigendum in: /10.3892/mmr.2018.8572

Authors:
- Jing Chen
- Dongming Zheng
- Hong Cui
- Sishi Liu
- Lijuan Zhang
- Caixia Liu
View Affiliations

Affiliations: Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110016, P.R. China
Published online on: November 7, 2017 https://doi.org/10.3892/mmr.2017.7998
Pages: 898-910
Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

The aim of the current study was to investigate the role of phospholipase C (PLC)γ/protein kinase C (PKC)/C‑kinase‑activated protein phosphatase‑1 (CPI‑17) signaling pathways in uterine smooth muscle during parturition. Samples of uterine tissue were collected from pregnant patients who underwent a caesarean section for preterm delivery, full‑term delivery with labor onset, full‑term delivery without labor onset, and from a non‑pregnant control group undergoing surgery for cervical intraepithelial neoplasia III. Immunohistochemistry, and western blotting were used to assess the association between TRPC3 levels and parturition and the influence of calcium ion channels. In addition, pregnant mice were used to explore the effect of uterine canonical transient receptor potential 3 (TRPC3) expression on the parturition‑triggering mechanism and PLCγ/PKC/CPI‑17 signaling pathways. Pregnant mouse uterine smooth muscle cells were cultivated, with and without TRPC3 silencing, and the expression levels of PLCγ, PKC and CPI‑17, the upstream and downstream factors of the TRPC3 pathway, were measured in pregnant mouse uterine smooth muscle cells, in order to provide a theoretical basis for the prevention and treatment of premature labor. In the preterm and full‑term without labor onset patient groups, the TRPC3 gene expression in the mSMCs was significantly overexpressed when compared with the non‑pregnant group (P<0.05); however, TRPC3 expression was not elevated in the full‑term with labor onset group, exhibiting no significant difference compared with the non‑pregnant group (P>0.05). During pregnancy, compared with the non‑pregnant controls, Cav1.2, Cav3.1 and Cav3.2 gene expression levels were markedly increased (P<0.05) in mSMCs from the preterm delivery group and the full‑term with labor onset group, however were non‑significantly increased in the full‑term without labor onset group. The level of TRPC3 was highest in the preterm group, while the levels of Cav1.2, Cav3.1 and Cav3.2 were highest in the full‑term with labor onset group. In the preterm, LPS‑treated preterm and full‑term groups, TRPC3, MAPK, ERK1/2, P‑ERK, Cav3.2, Cav3.1 and Cav1.2 were all expressed at higher levels than in the unfertilized group. In the LPS‑treated preterm group, the levels of TRPC3, MAPK, ERK1/2, P‑ERK, Cav3.2, Cav3.1 and Cav1.2 were increased compared with the preterm group. Furthermore, following transfection of small interfering TRPC3 (siTRPC3) into cells, it was demonstrated that the levels of TRPC3, PLCγ, PKC, CPI‑17, P‑CPI‑17, Cav1.2, Cav3.1 and Cav3.2 expression were lower in the LPS siTRPC3 group when compared with that of the LPS‑treated untransfected control group.

View Figures

View References

1	Senturk MB, Cakmak Y, Gündoğdu M, Polat M and Atac H: Does performing cesarean section after onset of labor has positive effect on neonatal respiratory disorders? J Matern Fetal Neonatal Med. 29:2457–2460. 2016.PubMed/NCBI
2	Hanley GE, Munro S, Greyson D, Gross MM, Hundley V, Spiby H and Janssen PA: Diagnosing onset of labor: A systematic review of definitions in the research literature. BMC Pregnancy Childbirth. 16:712016. View Article : Google Scholar : PubMed/NCBI
3	Ohno Y, Terauchi M, Tamakoshi K, Shiozaki A and Saito S: The risk factors for labor onset hypertension. Hypertens Res. 39:260–265. 2016. View Article : Google Scholar : PubMed/NCBI
4	Neal JL and Lowe NK: Physiologic partograph to improve birth safety and outcomes among low-risk, nulliparous women with spontaneous labor onset. Med Hypotheses. 78:319–326. 2012. View Article : Google Scholar : PubMed/NCBI
5	Kiesewetter B and Lehner R: Maternal outcome monitoring: Induction of labor versus spontaneous onset of labor-a retrospective data analysis. Arch Gynecol Obstet. 286:37–41. 2012. View Article : Google Scholar : PubMed/NCBI
6	Ijaiya MA, Adesina KT, Raji HO, Aboyeji AP, Olatinwo AO, Adeniran AS, Adebara IO and Isiaka-Lawal S: Duration of labor with spontaneous onset at the University of Ilorin Teaching Hospital, Ilorin, Nigeria. Ann Afr Med. 10:115–119. 2011. View Article : Google Scholar : PubMed/NCBI
7	Kapur NK, Qiao X, Paruchuri V, Mackey EE, Daly GH, Ughreja K, Morine KJ, Levine J, Aronovitz MJ, Hill NS, et al: Reducing endoglin activity limits calcineurin and TRPC-6 expression and improves survival in a mouse model of right ventricular pressure overload. J Am Heart Assoc. 3:pii: e000965. 2014. View Article : Google Scholar : PubMed/NCBI
8	Myeong J, Kwak M, Hong C, Jeon JH and So I: Identification of a membrane-targeting domain of the transient receptor potential canonical (TRPC)4 channel unrelated to its formation of a tetrameric structure. J Biol Chem. 289:34990–35002. 2014. View Article : Google Scholar : PubMed/NCBI
9	Dhar M, Wayman GA, Zhu M, Lambert TJ, Davare MA and Appleyard SM: Leptin-induced spine formation requires TrpC channels and the CaM kinase cascade in the hippocampus. J Neurosci. 34:10022–10033. 2014. View Article : Google Scholar : PubMed/NCBI
10	Zhang Y, Wang Y, Yang K, Tian L, Fu X, Wang Y, Sun Y, Jiang Q, Lu W and Wang J: BMP4 increases the expression of TRPC and basal [Ca2+]i via the p38MAPK and ERK1/2 pathways independent of BMPRII in PASMCs. PLoS One. 9:e1126952014. View Article : Google Scholar : PubMed/NCBI
11	Ilatovskaya DV, Levchenko V, Lowing A, Shuyskiy LS, Palygin O and Staruschenko A: Podocyte injury in diabetic nephropathy: Implications of angiotensin II-dependent activation of TRPC channels. Sci Rep. 5:176372015. View Article : Google Scholar : PubMed/NCBI
12	Yamada H, Yoshida M, Ito K, Dezaki K, Yada T, Ishikawa SE and Kakei M: Potentiation of glucose-stimulated insulin secretion by the GPR40-PLC-TRPC pathway in pancreatic β-cells. Sci Rep. 6:259122016. View Article : Google Scholar : PubMed/NCBI
13	Ziemba BP, Burke JE, Masson G, Williams RL and Falke JJ: Regulation of PI3K by PKC and MARCKS: Single-molecule analysis of a reconstituted signaling pathway. Biophys J. 110:1811–1825. 2016. View Article : Google Scholar : PubMed/NCBI
14	Ruiz-Loredo AY, López E and López-Colomé AM: Thrombin stimulates stress fiber assembly in RPE cells by PKC/CPI-17-mediated MLCP inactivation. Exp Eye Res. 96:13–23. 2012. View Article : Google Scholar : PubMed/NCBI
15	Hagel C, Dornblut C, Schulz A, Wiehl U, Friedrich RE, Huckhagel T, Mautner VF and Morrison H: The putative oncogene CPI-17 is up-regulated in schwannoma. Neuropathol Appl Neurobiol. 42:664–668. 2016. View Article : Google Scholar : PubMed/NCBI
16	Su W, Xie Z, Liu S, Calderon LE, Guo Z and Gong MC: Smooth muscle-selective CPI-17 expression increases vascular smooth muscle contraction and blood pressure. Am J Physiol Heart Circ Physiol. 305:H104–H113. 2013. View Article : Google Scholar : PubMed/NCBI
17	Jiang W, Li Z, Zhao W, Chen H, Wu Y, Wang Y, Shen Z, He J, Chen S, Zhang J and Fu G: Breviscapine attenuatted contrast medium-induced nephropathy via PKC/Akt/MAPK signalling in diabetic mice. Am J Transl Res. 8:329–341. 2016.PubMed/NCBI
18	Li W, Lv J, Wu J, Zhou X, Jiang L, Zhu X, Tu Q, Tang J, Liu Y, He A, et al: Maternal high-salt diet altered PKC/MLC20 pathway and increased ANG II receptor-mediated vasoconstriction in adult male rat offspring. Mol Nutr Food Res. 60:1684–1694. 2016. View Article : Google Scholar : PubMed/NCBI
19	Murthy KS, Zhou H, Grider JR, Brautigan DL, Eto M and Makhlouf GM: Differential signalling by muscarinic receptors in smooth muscle: m2-mediated inactivation of myosin light chain kinase via Gi3, Cdc42/Rac1 and p21-activated kinase 1 pathway, and m3-mediated MLC20 (20 kDa regulatory light chain of myosin II) phosphorylation via Rho-associated kinase/myosin phosphatase targeting subunit 1 and protein kinase C/CPI-17 pathway. Biochem J. 374:145–155. 2003. View Article : Google Scholar : PubMed/NCBI
20	Kolosova IA, Ma SF, Adyshev DM, Wang P, Ohba M, Natarajan V, Garcia JG and Verin AD: Role of CPI-17 in the regulation of endothelial cytoskeleton. Am J Physiol Lung Cell Mol Physiol. 287:L970–L980. 2004. View Article : Google Scholar : PubMed/NCBI
21	Eto M, Ohmori T, Suzuki M, Furuya K and Morita F: A novel protein phosphatase-1 inhibitory protein potentiated by protein kinase C. Isolation from porcine aorta media andaracterization. J Biochem. 18:1104–1107. 1995. View Article : Google Scholar
22	MacDonald JA, Eto M, Borman MA, Brautigan DL and Haystead TA: Dual Ser and Thr phosphorylation of CPI-17, an inhibitor of myosin phosphatase, by MYPT associated kinase. FEBS Lett. 493:91–94. 2001. View Article : Google Scholar : PubMed/NCBI
23	Zemlickova E, Johannes FJ, Aitken A and Dubois T: Association of CPI-17 with protein kinase C and casein kinase I. Biochem Biophys Res Commun. 316:39–47. 2004. View Article : Google Scholar : PubMed/NCBI
24	Kitazawa T, Semba S, Huh YH, Kitazawa K and Eto M: Nitric oxide-induced biphasic mechanism of vascular relaxation via dephosphorylation of CPI-17 and MYPT1. J Physiol. 587:3587–3603. 2009. View Article : Google Scholar : PubMed/NCBI
25	Sakai H, Hirano T, Takeyama H, Chiba Y and Misawa M: Acetylcholine-induced phosphorylation of CPI-17 in rat bronchial smooth muscle: The roles of Rho-kinase and protein kinase C. Can J Physiol Pharmacol. 83:375–381. 2005. View Article : Google Scholar : PubMed/NCBI
26	Sakai H, Chiba Y and Misawa M: Augmentation of endothelin-1-induced phosphorylation of CPI-17 and myosin light chain in bronchial smooth muscle from airway hyperresponsive rats. Biol Pharm Bull. 29:1897–1899. 2006. View Article : Google Scholar : PubMed/NCBI
27	Sladek SM, Magness RR and Conrad KP: Nitric oxide and pregnancy. Am J Physiol. 272:R441–R463. 1997.PubMed/NCBI