Cell signaling pathways in the adrenal cortex: Links to stem/progenitor biology and neoplasia

Penny, Morgan K.; Finco, Isabella; Hammer, Gary D.

doi:10.1016/j.mce.2016.12.005

Cited by 25 publications

(14 citation statements)

References 148 publications

(223 reference statements)

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“…Shh is a member of hedgehog signaling pathway with well known mitogenic and morphogenic function during embryonic development [ Ingham et al, 2011 , Laufer et al, 2012 ]. Recent studies demonstrate implication of Shh signaling in regulation of adult stem cells involved in physiological regeneration of adult tissues [ Shin et al, 2011 , Peng et al, 2013 , Petrova and Joyner, 2014 , Penni et al, 2017 , Das et al, 2020 ]. Low proliferation rate in adrenal cortex of Shh mutants supports the idea that Shh is implicated in regulation of adult tissue homeostasis [ Ching and Vilain, 2009 ].…”

Section: Discussionmentioning

confidence: 99%

Developmental exposure to endocrine disrupter dichlorodiphenyltrichloroethane alters transcriptional regulation of postnatal morphogenesis of adrenal zona fasciculata

Yaglova

Обернихин

Назимова

2020

Saudi Journal of Biological Sciences

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The present study is aimed to validate expression of transcriptional factors mediating postnatal development of adrenal zona fasciculata in rats exposed to low doses of endocrine disrupter dichlorodiphenyltrichloroethane prenatally and postnatally. Histological and immunohistochemical examination of the adrenals was performed. Impaired blood circulation, dystrophy and cell death were found in zona fasciculata of pubertal rats after developmental exposure to low doses of dichlorodiphenyltrichloroethane. Reparation of zona fasciculata was associated with increased number of Sonic hedgehog- and Oct4-expressing adrenal cortical cells but not in areas of regeneration. These data suggest that cell death may promote upregulation of factors inducing and maintaining pluripotent state in fasciculata cells for restoration of tissue homeostasis. Termination of growth of the adrenals after puberty was associated with upregulation of antiproliferative factor Hhex and decrease of cell proliferation. Dichlorodiphenyltrichloroethane exposure disrupted transcriptional control of cell proliferation by downregulation of Hhex expression in fasciculata cells. Decrease of proliferation in the exposed rats was mediated by inhibition of Sonic hedgehog and Oct4 expression and suppression of canonical Wnt signaling. The present study elucidated an alternative mechanism of proliferation control activated by endocrine disrupter dichlorodiphenyltrichloroethane through transition of fasciculata cells from pluripotent state and higher proliferative potential to differentiation. Activation of the alternative mechanism of growth control may probably affect maintenance of tissue homeostasis of zona fasciculata in postnatal development.

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Section: Discussionmentioning

confidence: 99%

Developmental exposure to endocrine disrupter dichlorodiphenyltrichloroethane alters transcriptional regulation of postnatal morphogenesis of adrenal zona fasciculata

Yaglova

Обернихин

Назимова

2020

Saudi Journal of Biological Sciences

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“…The Shh signaling pathway plays crucial roles in embryonic patterning and adult tissue homeostasis[13,14]. It was reported that the Shh signaling pathway was activated aberrantly in tumorigenesis and development of gastrointestinal, pancreatic, breast, lung, ovarian cancers and so on[15-18].…”

Section: Introductionmentioning

confidence: 99%

Dbx2 exhibits a tumor-promoting function in hepatocellular carcinoma cell lines via regulating Shh-Gli1 signaling

Zhang

et al. 2019

WJG

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BACKGROUND Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide. HCC patients suffer from a high mortality-to-incidence ratio and low cure rate since we still have no specific and effective treatment. Although tremendous advances have been made in the investigation of HCC, the specific mechanisms of the progression of this disease are still only partially established. Hence, more research is needed to elucidate the underlying potential mechanisms to develop effective strategies for HCC. AIM To determine the role of developing brain homeobox 2 (Dbx2) gene in promoting the development of HCC. METHODS Dbx2 expression in clinical specimens and HCC cell lines was detected by Western blot (WB) and immunohistochemistry. Gain and loss of Dbx2 function assays were performed in vitro and in vivo . Cell viability assays were used to investigate cell growth, flow cytometry was employed to assess cell cycle and apoptosis, and trans-well assays were conducted to evaluate cell migration, invasion, and metastasis. The expression of key molecules in the sonic hedgehog (Shh) signaling was determined by WB. RESULTS Compared to matched adjacent non-tumorous tissues, Dbx2 was overexpressed in 5 HCC cell lines and 76 surgically resected HCC tissues. Dbx2 overexpression was correlated with large tumor size. Both gain and loss of function assays indicated that Dbx2 promoted HCC cell proliferation by facilitating the transition from G1 to S phase, attenuating apoptosis and promoted HCC proliferation, migration, and invasion in vitro and in vivo . Mechanistically, Dbx2 modulated Shh signaling by enhancing FTCH1 and GLi1 expression in HCC cells that overexpressed Dbx2, which was reversed in HCC cells with Dbx2 knockdown. CONCLUSION Our results indicate that Dbx2 is significantly upregulated in HCC tissues and plays significant roles in proliferation and metastasis of HCC cells by activating the Shh pathway.

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“…However, the progenitor niche composition and cell identity, as well as the molecular mechanisms and paracrine factors involved in controlling the organ homeostasis, are still far from being completely understood. Indeed, any alteration in these processes at different developmental stages may underlie the functional hormonal defects and tumor development later occurring in the adrenal organ history (15,16). The current knowledge about the development and neonatal remodeling of the adrenal gland is limited, and nearly all models has been developed in animals (15), with only very scarce functional data available from studies of human fetal adrenals (17,18).…”

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confidence: 99%

Human fetal adrenal cells retain age‐related stem‐ and endocrine‐differentiation potential in culture

et al. 2018

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The adrenal gland is a multiendocrine organ with a steroidogenic mesenchymal cortex and an inner catecholamine‐producing medulla of neuroendocrine origin. After embryonic development, this plastic organ undergoes a functional postnatal remodeling. Elucidating these complex processes is pivotal for understanding the early bases of functional endocrine disorders and tumors affecting the mature gland. We developed an in vitro human adrenal cell model derived from fetal adrenal specimens at different gestational ages, consisting of neuroendocrine and cortical components and expressing the zona and functional markers of the original fetal organ. These cortical and neuroendocrine progenitor cells retain in vitro an intrinsic gestational‐age–related differentiation and functional program. In vitro these cells spontaneously form 3‐dimensional structure organoids with a structure similar to the fetal gland. The organoids show morphofunctional features and adrenal steroidogenic factor, steroid acute regulatory, cytochrome‐P450‐17A1, dosage‐sensitive, sex‐reversal, adrenal hypoplasia–critical region on chromosome X protein, NOTCH1, and nephroblastoma overexpressed/cysteine‐rich protein 61/connective tissue growth factor/nephroblastoma overexpressed gene‐3; stem (BMI1, nestin); and chromaffin (chromogranin A, tyrosine hydroxylase) markers similar to those of the populations of origin. This in vitro human adrenal system represents a unique but preliminar model for investigating the pathophysiological processes underlying physiologic adrenal remodeling and pathologic alterations involved in organ hypo‐ and hyperplasia and cancer.—Poli, G., Sarchielli, E., Guasti, D., Benvenuti, S., Ballerini, L., Mazzanti, B., Armignacco, R., Cantini, G., Lulli, M., Chortis, V., Arlt, W., Romagnoli, P., Vannelli, G. B., Mannelli, M., Luconi, M. Human fetal adrenal cells retain age‐related stem‐and endocrine‐differentiation potential in culture. FASEB J. 33, 2263–2277 (2019). http://www.fasebj.org

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Cell signaling pathways in the adrenal cortex: Links to stem/progenitor biology and neoplasia

Cited by 25 publications

References 148 publications

Developmental exposure to endocrine disrupter dichlorodiphenyltrichloroethane alters transcriptional regulation of postnatal morphogenesis of adrenal zona fasciculata

Developmental exposure to endocrine disrupter dichlorodiphenyltrichloroethane alters transcriptional regulation of postnatal morphogenesis of adrenal zona fasciculata

Dbx2 exhibits a tumor-promoting function in hepatocellular carcinoma cell lines via regulating Shh-Gli1 signaling

Human fetal adrenal cells retain age‐related stem‐ and endocrine‐differentiation potential in culture

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