Genetic regulatory networks of nephrogenesis: Deregulation of <i>WT1</i> splicing by benzo(a)pyrene

Ramos, Kenneth S.; Nañez, Adrian

doi:10.1002/bdrc.20148

Cited by 8 publications

(6 citation statements)

References 68 publications

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“…Chemicals, especially endocrine disruptors like some polycyclic aromatic hydrocarbons (PAHs) can inhibit IGC activity in some organs and human placenta. 51,52 Another possible explanation was associated with interference of pollutants with thyroxine binding to transthyretin, DNA damages by toxic pollutants, and/ or occurrence of respiratory diseases and slower lung function growth. 29,[53][54][55] Increased acute lower respiratory infection (ALRI)…”

Section: Discussionmentioning

confidence: 99%

Association of solid fuel use with risk of stunting in children living in China

et al. 2019

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Stunting adversely affects physical and mental outcomes of children. It has not been examined whether household air pollution from solid fuel combustion is a risk factor for stunting in children. In a total of 41,439 children aged 6‐17 across China, height was measured using a unified protocol. Multivariable linear regression models and logistic regression models were used to assess the associations of solid fuel use for cooking/heating with stunting in children. Adjusted for covariates, cooking/heating with solid fuel was significantly associated with a lower z‐score for height for age and sex (β = −0.21 [−0.32 to −0.09] and −0.17 [−0.31 to −0.03], respectively) and an increased risk of stunting with an estimated ORs of 1.34 [1.07~1.68] and 1.37 [1.02~1.83], respectively. The risk of stunting associated with solid fuel use was statistically significant in high‐age children. And the effect was greater on girls than on boys, though the difference was not statistically significant. Our study suggested that Chinese children living in households using solid fuel had a significantly higher risk of stunting than those living in households using cleaner fuel.

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Section: Discussionmentioning

confidence: 99%

Association of solid fuel use with risk of stunting in children living in China

et al. 2019

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“…This hypothesis is consistent with the notion that genomic changes during critical developmental periods defines susceptibility to disease and set the stage for adult-onset disease (Barker, 1995; Beaulac-Baillargeon and Desrosiers, 1987). The impact on genetic regulation in the embryo is likely not restricted to the developing kidney and may in fact contribute to morphogenetic deficits in other tissues where AHR and/or WT1 play important roles (for review see (Ramos and Nanez, 2009) and references herein). For instance, AHR -/- mice present defects in vascular structures, extramedular hematopoiesis, reduced liver weight, cardiac hypertrophy, and hypertension (Fernandez-Salguero et al, 1995; Lahvis et al, 2000; Lahvis et al, 2005; Lund et al, 2003; Lund et al, 2006; Schmidt et al, 1996).…”

Section: Discussionmentioning

confidence: 99%

Epigenetic control of embryonic renal cell differentiation by L1 retrotransposon

Ramos

Montoya-Durango

Teneng

et al. 2011

Birth Defects Research

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Background L1 retroelements may play a central role in morphogenesis through epigenetic mechanisms involving recruitment of chromatin modifying protein complexes. Retroelements are repressed in terminally differentiated cells, and highly active in embryonic, undifferentiated, and transformed cells. It is not clear if the modulation of differentiation by L1 is a “cause” or “effect”. The aim of this study was to determine if murine embryonic kidney cells of clonal origin (mK4 cells) harbor retrotransposition events upon ectopic expression of L1, and the impact of L1 on embryonic kidney cell differentiation. Given that L1 is reactivated by AHR ligands, we also sought to investigate the effects of benzo(a)pyrene (BaP) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on the genetic network of mK4 cells. Methods mK4 cells overexpressing human LIRP were assessed for changes in proliferation and expression of molecular markers of cellular differentiation. Results L1RP increased proliferation rates and markedly downregulated differentiation programming in mK4 cells. These genetic alterations were recapitulated by exogenous activation of L1 by AHR ligands. Conclusion L1 regulates nephrogenesis in vitro via both insertional and non-insertional mechanisms that disrupt mesenchymal to epithelial transition. Thus, a feedback loop involving L1, WT1 and AHR may play a role in regulation of kidney morphogenesis.

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“…25 Full length LINE-1 includes a 5′-untranslated region (UTR) that contains regulatory sequences that recognize proteins such as yin yang 1 (YY1), runt-related transcription factor 3 (RUNX-3), and E2 factor/retinoblastoma tumor suppressor protein (E2F/RB). 28 The latter is particularly significant in light of work completed by our group establishing this complex as one of the master effectors of LINE-1 epigenetic silencing. 29 The silencing of LINE-1 is executed via DNA methylation through a complex process that involves assembly of nucleosome remodeling deacetylase (NuRD) corepressor complexes.…”

Section: Long Interspersed Nuclear Element-1 As a Therapeutic Targetmentioning

confidence: 99%

“…The finding that EMT programming involves the reactivation of LINE-1 is in keeping with the role of these genetic sequences in modulating genomes through insertional mutation or chromatin rearrangements. 28,36 The linkage between EMT programming and malignancy in patients with COPD may thus be related to the modulation of EMT programming by LINE-1.…”

Section: Line-1 Activation Is Linked With Lung Cancer and May Serve Amentioning

confidence: 99%

Precision prevention: A focused response to shifting paradigms in healthcare

Ramos

Bowers

Tavera-Garcia

et al. 2019

Exp Biol Med (Maywood)

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Human health and disease are defined at the intersection of molecules, environment, and lifestyle, which combined determine phenotypic outcomes. To date, most clinical applications in the precision medicine space have focused on DNA, with lesser attention given to the biology encoded by RNA molecules, or the complexity of biological regulation at the level of proteins and metabolites. The totality of this information must be integrated in ways that allow for implementation of knowledge-based health promotion and prevention strategies that can help address current limitations in healthcare delivery. This review describes recent advances in the development of diagnostic tools for early detection and stratification of individuals suffering from chronic obstructive pulmonary disease and their heightened risk for the development of lung malignancies. Impact statement The study of LINE-1 retroelements and their role in the pathogenesis of diseases of the lung such as COPD and lung cancer may provide valuable diagnostic and therapeutic tools to identify pre-emptively individuals at risk of pulmonary disease progression. Limited information is presently available on the role of LINE-1 in the regulation of disease phenotypes and the development of novel therapeutics designed to curtail LINE-1-mediated pathogenesis. Successful implementation of precision prevention strategies may help to spare those impacted by obstructive pulmonary disease from continued deterioration, while realizing significant cost savings and improved quality of healthcare.

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Genetic regulatory networks of nephrogenesis: Deregulation of WT1 splicing by benzo(a)pyrene

Cited by 8 publications

References 68 publications

Association of solid fuel use with risk of stunting in children living in China

Association of solid fuel use with risk of stunting in children living in China

Epigenetic control of embryonic renal cell differentiation by L1 retrotransposon

Precision prevention: A focused response to shifting paradigms in healthcare

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