Hypoxic preconditioning induces elevated expression of stanniocalcin-1 in the heart

Westberg, Johan A.; Serlachius, Martina; Lankila, Petri; Andersson, Leif C.

doi:10.1152/ajpheart.00017.2007

Cited by 44 publications

(37 citation statements)

References 39 publications

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“…Previous studies showed that STC-1 was upregulated in cancer cells during hypoxia [16, 17, 38]. Our results also demonstrated that MSCs decreased apoptosis in co-cultures with a line of pulmonary epithelial cells in which apoptosis was produced by hypoxia under acidic conditions.…”

Section: Discussionsupporting

confidence: 83%

“…In sections of mouse kidney, STC-1 was present throughout the cytoplasm with apparent enrichment within mitochondria [39]. In cardiomyocytes over-expressing a STC-1-FLAG fusion protein, STC-1 was seen in mitochondria [17]. STC-1 was also found in the nucleus in cardiomyocytes [40] and in mouse lactiferous duct cells during pregnancy [41].…”

Section: Discussionmentioning

confidence: 99%

“…STC-1 upregulation has been observed in multiple models of injury, including the ischemic brain [42], obstructed kidney [37], and the hypoxia preconditioned heart and brain [17]. Furthermore, the STC-1 gene is readily activated by multiple cytokines [36, 37, 43].…”

Section: Discussionmentioning

confidence: 99%

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Multipotent stromal cells are activated to reduce apoptosis in part by upregulation and secretion of stanniocalcin-1

et al. 2009

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Multipotent stromal cells (MSCs) have been shown to reduce apoptosis in injured cells by secretion of paracrine factors, but these factors were not fully defined. We observed that co-culture of MSCs with previously UV irradiated fibroblasts reduced apoptosis of the irradiated cells, but fresh MSC conditioned media was unable reproduce the effect. Comparative Microarray analysis of MSCs grown in the presence or absence of UV irradiated fibroblasts demonstrated that the MSCs were activated by the apoptotic cells to increase synthesis and secretion of stanniocalcin-1 (STC-1), a peptide hormone that modulates mineral metabolism and has pleiotrophic effects that have not been fully characterized. We showed that STC-1 was required but not sufficient for reduction of apoptosis of UV-irradiated fibroblasts. In contrast, we demonstrated that MSC-derived STC-1 was both required and sufficient for reduction of apoptosis of lung cancer epithelial cells made apoptotic by incubation at low pH in hypoxia. Our data demonstrate that STC-1 mediates the anti-apoptotic effects of MSCs in two distinct models of apoptosis in vitro.

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Section: Discussionsupporting

confidence: 83%

Section: Discussionmentioning

confidence: 99%

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Multipotent stromal cells are activated to reduce apoptosis in part by upregulation and secretion of stanniocalcin-1

et al. 2009

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“…Recently, multiple functions of mammalian STC1, except for the primarily reported function in fish of maintaining calcium or phosphorus homeostasis, have been demonstrated. These include ischemic tolerance in the brain or heart [40,41], regulation of cellular metabolism by targeting mitochondria [42,43] and association with angiogenesis in endothelial cells [44]. Quite recently, the presence of endometrial STC1 in pregnant mares was reported [45].…”

Section: Expression Of Stanniocalcin-1 In the Equine Endometriummentioning

confidence: 99%

Production of Calcium Maintenance Factor Stanniocalcin-1 (STC1) by the Equine Endometrium During the Early Pregnant Period

et al. 2011

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Abstract.A factor responsible for progression to pregnancy establishment in the mare has not been definitively characterized. To identify factors possibly involved in the establishment of equine pregnancy, the endometrium was collected from day 13 (day 0=day of ovulation) cyclic and day 13, 19 and 25 pregnant animals. From initial subtractive hybridization studies, a calcium regulating factor, Stanniocalcin-1 (STC1) mRNA, was found as a candidate molecule expressed uniquely in the pregnant endometrium. Endometrial expression of STC1 mRNA was noted on day 19 and was markedly increased in the day 25 gravid endometrium. STC1 protein was found in the extracts of day 25 gravid endometrium and immunochemically localized in the uterine glands. In addition, STC1 protein was detected in uterine flushing media collected from day 25 pregnant mares. High concentrations of estradiol-17β (E2) were detected in day 25 conceptuses. E2 levels were much higher in the gravid endometrium than in other regions, whereas progesterone levels did not differ among the samples from different endometrial regions. Expression of STC1 mRNA, however, was not significantly upregulated in cultured endometrial explants treated with various concentrations of E2 (0.01-100 ng/ml) with or without 10 ng/ml progesterone. These results indicate that an increase in STC1 expression appears to coincide with capsule disappearance in the conceptus, and suggest that STC1 from the uterine glands likely plays a role in conceptus development during the pregnancy establishment period in the mare. Key words: Endometrium, Equine, Estradiol-17β, Stanniocalcin-1 (STC1), Uterine secretion (J. Reprod. Dev. 57: [203][204][205][206][207][208][209][210][211] 2011) he establishment of equine pregnancy is a unique and long process, during which a series of physical and possibly biochemical interactions are required between the conceptus and uterus. The equine conceptus first enters into the uterus on days 6-8 of pregnancy (day 0=day of ovulation) [1] and then begins to transmigrate throughout the entire uterine body and horns until approximately day 16 of pregnancy [2][3][4]. The frequency at which a conceptus moves from one uterine horn to another increases up to 10-20 times per day [5]. The conceptus ceases migration and lodges at the caudal portion of one of the uterine horns, known as "fixation", on approximately days 16-18 of pregnancy [2]. Between days 11 and 16 of pregnancy, the conceptus rapidly expands its volume, but keeps its spherical shape surrounded by a unique, smooth structure called a "capsule" [6,7] that emerges beneath the zona pellucida on days 6-8 of pregnancy. The capsule is an acellular mucin-like glycoprotein [8] that is structurally strong and is considered essential for the survival of the conceptus and continuation of pregnancy [9,10]. Together with peristaltic myometrial contractions, the capsule is likely to give motility to the conceptus, although the precise stimulus for conceptus migration is unknown. Thereafter, the capsule disappears by d...

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“…STC1 has been identified as one of the genes regulated by HIF-1 [11]. STC1 expression induces ischemia tolerance in mouse brains and hearts, suggesting its possible role in cell survival under hypoxic conditions [12,13]. STC1 also reduces the number of apoptotic lung cancer epithelial cells following hypoxia [14], which suggests that the induction of STC1 in a hypoxic microenvironment plays an important role in tumor progression [9,11,15].…”

Section: Introductionmentioning

confidence: 99%

Stanniocalcin-1 is induced by hypoxia inducible factor in rat alveolar epithelial cells

Ito

Zemans

Correll

et al. 2014

Biochemical and Biophysical Research Communications

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Alveolar type II (ATII) cells remain differentiated and express surfactant proteins when cultured at an air-liquid (A/L) interface. When cultured under submerged conditions, ATII cells dedifferentiate and change their gene expression profile. We have previously shown that gene expression under submerged conditions is regulated by hypoxia inducible factor (HIF) signaling due to focal hypoxia resulting from ATII cell metabolism. Herein, we sought to further define gene expression changes in ATII cells cultured under submerged conditions. We performed a genome wide microarray on RNA extracted from rat ATII cells cultured under submerged conditions for 24–48 h after switching from an A/L interface. We found significant alterations in gene expression, including upregulation of the HIF target genes stanniocalcin-1 (STC1), tyrosine hydroxylase (Th), enolase (Eno) 2, and matrix metalloproteinase (MMP) 13, and we verified upregulation of these genes by RT-PCR. Because STC1, a highly evolutionarily conserved glycoprotein with anti-inflammatory, anti-apoptotic, anti-oxidant, and wound healing properties, is widely expressed in the lung, we further explored the potential functions of STC1 in the alveolar epithelium. We found that STC1 was induced by hypoxia and HIF in rat ATII cells, and this induction occurred rapidly and reversibly. We also showed that recombinant human STC1 (rhSTC1) enhanced cell motility with extended lamellipodia formation in alveolar epithelial cell (AEC) monolayers but did not inhibit the oxidative damage induced by LPS. We also confirmed that STC1 was upregulated by hypoxia and HIF in human lung epithelial cells. In this study, we have found that several HIF target genes including STC1 are upregulated in AECs by a submerged condition, that STC1 is regulated by hypoxia and HIF, that this regulation is rapidly and reversibly, and that STC1 enhances wound healing moderately in AEC monolayers. However, STC1 did not inhibit oxidative damage in rat AECs stimulated by LPS in vitro. Therefore, alterations in gene expression by ATII cells under submerged conditions including STC1 were largely induced by hypoxia and HIF, which may be relevant to our understanding of the pathogenesis of various lung diseases in which the alveolar epithelium is exposed to relative hypoxia.

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Hypoxic preconditioning induces elevated expression of stanniocalcin-1 in the heart

Cited by 44 publications

References 39 publications

Multipotent stromal cells are activated to reduce apoptosis in part by upregulation and secretion of stanniocalcin-1

Multipotent stromal cells are activated to reduce apoptosis in part by upregulation and secretion of stanniocalcin-1

Production of Calcium Maintenance Factor Stanniocalcin-1 (STC1) by the Equine Endometrium During the Early Pregnant Period

Stanniocalcin-1 is induced by hypoxia inducible factor in rat alveolar epithelial cells

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