Alteration in Endometrial Proteins during Early- and Mid-Secretory Phases of the Cycle in Women with Unexplained Infertility

Manohar, Murli; Khan, Huma; Sirohi, Vijay Kumar; Das, Vinita; Agarwal, Anjoo; Pandey, Anshuman; Siddiqui, Waseem Ahmad; Dwivedi, Anila

doi:10.1371/journal.pone.0111687

Cited by 32 publications

(22 citation statements)

References 65 publications

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“…Sorcin is important for endometrium development and embryo implantation: it is downregulated in the mid-secretory (receptive) endometrium of women with unexplained infertility with respect to fertile women, and mediates endometrial angiogenesis, endothelial proliferation, migration, and invasion via regulation of the vascular endothelial growth factor (VEGF) pathway involving the vascular endothelial growth factor receptor 2 (VEGFR2), phosphatidylinositol 3-kinase (PI3K), Akt, and nitric oxide synthase (NOS) expression, possibly by regulating calcium homeostasis [77,78].…”

Section: Sorcin Under Cellular Stressing Conditions and In Pathologiesmentioning

confidence: 99%

“…Sorcin induces gastric tumor cell migration and invasion; sorcin silencing downregulates the expression of cathepsin Z, matrix metalloproteinases 2 and 9 (MMP2 and MMP9), and signal transducer and activator of transcription 3 (STAT3), resulting in the suppression of cancer growth and metastasis [77]. Sorcin overexpression facilitates cell migration, invasion, and epithelial-…”

Section: Sorcin Metastatization and Emtmentioning

confidence: 99%

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Roles of Sorcin in Drug Resistance in Cancer: One Protein, Many Mechanisms, for a Novel Potential Anticancer Drug Target

Battista

Fiorillo

Chiarini

et al. 2020

Cancers

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The development of drug resistance is one of the main causes of failure in anti-cancer treatments. Tumor cells adopt many strategies to counteract the action of chemotherapeutic agents, e.g., enhanced DNA damage repair, inactivation of apoptotic pathways, alteration of drug targets, drug inactivation, and overexpression of ABC (Adenosine triphosphate-binding cassette, or ATP-binding cassette) transporters. These are broad substrate-specificity ATP-dependent efflux pumps able to export toxins or drugs out of cells; for instance, ABCB1 (MDR1, or P-glycoprotein 1), overexpressed in most cancer cells, confers them multidrug resistance (MDR). The gene coding for sorcin (SOluble Resistance-related Calcium-binding proteIN) is highly conserved among mammals and is located in the same chromosomal locus and amplicon as the ABC transporters ABCB1 and ABCB4, both in human and rodent genomes (two variants of ABCB1, i.e., ABCB1a and ABCB1b, are in rodent amplicon). Sorcin was initially characterized as a soluble protein overexpressed in multidrug (MD) resistant cells and named “resistance-related” because of its co-amplification with ABCB1. Although for years sorcin overexpression was thought to be only a by-product of the co-amplification with ABC transporter genes, many papers have recently demonstrated that sorcin plays an important part in MDR, indicating a possible role of sorcin as an oncoprotein. The present review illustrates sorcin roles in the generation of MDR via many mechanisms and points to sorcin as a novel potential target of different anticancer molecules.

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Section: Sorcin Under Cellular Stressing Conditions and In Pathologiesmentioning

confidence: 99%

Section: Sorcin Metastatization and Emtmentioning

confidence: 99%

Roles of Sorcin in Drug Resistance in Cancer: One Protein, Many Mechanisms, for a Novel Potential Anticancer Drug Target

Battista

Fiorillo

Chiarini

et al. 2020

Cancers

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“…In the tree shrew, many small arteries in the endometrium, and small glands in anestrus develop into long tube glands in estrus (Fig. 7H-J), which is similar those in secretory phase of human uterus (Dixon et al 2014;Manohar et al 2014;Spencer 2014). It also displays that tree shrew could be a suitable non-monkey primate animal model for the elucidation of biological functions of uterine glands during the reproductive cycle and pregnancy (Hawkins and Matzuk 2008;Spencer 2014).…”

Section: Discussionmentioning

confidence: 52%

Revealing histological and morphological features of female reproductive system in tree shrew (Tupaia belangeri)

Zhong¹,

Zhang²,

Xing

et al. 2017

Zoomorphology

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The tree shrew has been used as a primate animal model in neuroscience studies but it has only rarely been employed in the study of reproductive systems. This is mainly because we know very little about the histological features of reproductive organs of the tree shrew. In this study, we have systematically analyzed the histology of reproductive organs of tree shrew, in comparison with human organs. The uterus of female tree shrew is uterus biomes unicolis, which is connected with an enveloped ovary through a thin fallopian tube. Histologically, the fallopian tube consists of folded mucosa, muscularis and serosa. Like other mammalian animals, the different developmental stages (primordial, primary, secondary and Graafian follicles) of ovarian follicles including inner oocyte and outer granulosa cells are embedded in the cortex. The luminal endometrium, middle muscular myometrium and serosa constitute the wall of uterus of tree shrew. The uterine endometrium contains simple columnar ciliated cells and goblet cells, and there are rich uterine glands in underlying stroma. Furthermore, these glands of tree shrew are round and smaller during anestrus, and become much longer when they are in estrus. The uterine endometrium in younger animals was less developed when compared to a mature tree shrew. Compared to human uterine endometrium, the histological features of tree shrew are very similar, indicating that it could potentially be good primate animal model for studying the diseases in reproductive system

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“…Some reports have also defined the involvement of TPPP3 in mares' reproductive system (Klein et al 2010, Hayes et al 2012. In our previous study, a decreased expression of TPPP3 in the mid-secretory phase of an infertile endometrium was observed (Manohar et al 2014a). More recently, we have demonstrated the functional role of TPPP3 during embryo implantation in mice and its relation with β-catenin (Shukla et al 2018).…”

Section: Introductionmentioning

confidence: 69%

Inhibition of TPPP3 attenuates β-catenin/NF-κB/COX-2 signaling in endometrial stromal cells and impairs decidualization

Shukla

Kaushal

Sankhwar

et al. 2019

Journal of Endocrinology

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Embryo implantation and decidualization are critical events that occur during early pregnancy. Decidualization is synchronized by the crosstalk of progesterone and the cAMP signaling pathway. Previously, we confirmed the role of TPPP3 during embryo implantation in mice, but the underlying role and mechanism of TPPP3 in decidualization has not yet been understood. The current study was aimed to investigate the role of TPPP3 in decidualizationin vivoandin vitro. Forin vivoexperiments, decidual reaction was artificially induced in the uteri of BALB/c mice. TPPP3 was found to be highly expressed during decidualization, whereas in the uteri receiving TPPP3 siRNA, decidualization was suppressed and the expression of β-catenin and decidual marker prolactin was reduced. In human endometrium, TPPP3 protein was found to be predominantly expressed in the mid-secretory phase (LH+7). In the primary culture of human endometrial stromal cells (hESCs), TPPP3 siRNA knockdown inhibited stromal-to-decidual cell transition and decreased the expression of the decidualization markers prolactin andIGFBP-1. Immunofluorescence and immunoblotting experiments revealed that TPPP3 siRNA knockdown suppressed the expression of β-catenin, NF-κB and COX-2 in hESCs during decidualization. TPPP3 inhibition also decreased NF-kB nuclear accumulation in hESCs and suppressed NF-κB transcriptional promoter activity. COX-2 expression was significantly decreased in the presence of a selective NF-kB inhibitor (QNZ) implicating that NF-kB is involved in COX-2 expression in hESCs undergoing decidualization. TUNEL assay and FACS analysis revealed that TPPP3 knockdown induced apoptosis and caused loss of mitochondrial membrane potential in hESCs. The study suggested that TPPP3 plays a significant role in decidualization and its inhibition leads to the suppression of β-catenin/NF-κB/COX-2 signaling along with the induction of mitochondria-dependent apoptosis.

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Alteration in Endometrial Proteins during Early- and Mid-Secretory Phases of the Cycle in Women with Unexplained Infertility

Cited by 32 publications

References 65 publications

Roles of Sorcin in Drug Resistance in Cancer: One Protein, Many Mechanisms, for a Novel Potential Anticancer Drug Target

Roles of Sorcin in Drug Resistance in Cancer: One Protein, Many Mechanisms, for a Novel Potential Anticancer Drug Target

Revealing histological and morphological features of female reproductive system in tree shrew (Tupaia belangeri)

Inhibition of TPPP3 attenuates β-catenin/NF-κB/COX-2 signaling in endometrial stromal cells and impairs decidualization

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