Immunohistochemical detection of vimentin in pancreatic islet β- and α-cells of macrosomic infants of diabetic and nondiabetic mothers

Krivova, Yuliya; Proshchina, Alexandra; Barabanov, V. M.; Barinova, I V; Saveliev, S. V.

doi:10.1016/j.earlhumdev.2017.12.009

Cited by 5 publications

(2 citation statements)

References 34 publications

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“…As a direct consequence of lowered concentration of b-TFs, de-repression of a subset of mesenchymal genes is elicited and an EMT process is induced. As we are witnessing a growing body of evidence indicating induction of the EMT marker Vim in b-cells of diabetic subjects (73)(74)(75)(76), our data provide mechanistic insights into this EMT process in T2D.…”

Section: Smarca4/brg1 Is a Target Of Mir-7 In B-cellsmentioning

confidence: 79%

β-cell dedifferentiation is associated with epithelial-mesenchymal transition triggered by miR-7-mediated repression of mSwi/Snf complex

Mak

Ohlen

Wang

et al. 2019

Preprint

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b-cell dedifferentiation has been revealed as a pathological mechanism underlying pancreatic dysfunction in diabetes. However, little is known on the genetic and epigenetic changes linked with the dedifferentiation of b-cells. We now report that b-cell dedifferentiation is associated with epithelial to mesenchymal transition (EMT) triggered by miR-7-mediated repression of Smarca4/Brg1 expression, a catalytic subunit of the mSwi/Snf chromatin remodeling complexes essential for b-cell transcription factors (b-TFs) activity. miR-7-mediated repression of Brg1 expression in diabetes causes an overall compaction of chromatin structure preventing b-TFs from accessing and transactivating genes maintaining the functional and epithelial identity of b-cells. Concomitantly, loss of b-cell identity impairs the ability of b-TFs Pdx1, Nkx6-1, Neurod1 to repress non-b-cell genes enriched selectively in mesenchymal cells leading to EMT, change in islet microenvironment, and fibrosis. Remarkably, anti-EMT agents normalized glucose tolerance of diabetic mice, thus revealing mesenchymal reprogramming of b-cells as a novel therapeutic target in diabetes. This study sheds light on the genetic signature of dedifferentiated b-cells and highlights how loss of mSwi/Snf activity in diabetes initiating a step-wise remodeling of epigenetic landscapes of b-cells leading to the induction of an EMT process reminiscent of a response to tissue injury. specific miR-7 overexpressing mouse model (Tg7) which develops early-onset diabetes due to b-cell dedifferentiation (32). Conversely, how elevated miR-7 levels in diabetes impair b-cell identity remains unclear. By profiling gene expression and open chromatin regions of Tg7 islets, we now report that loss of b-cell identity triggers an islet injury response characterized by an epithelial to mesenchymal transition (EMT) process in both mouse and humans. Elevated miR-7 levels trigger the dedifferentiation of mature b-cells through the repression of Brg1/Smarca4, a catalytic subunit of mSwi/Snf chromatin remodelling complexes required for the transactivation lineagespecific and epithelial genes by b-cell transcription factors (b-TF) function. Our findings highlight how dysregulation miRNA networks can compromise the functional and epithelial identity of b-cells and trigger an EMT-like reprogramming process with therapeutic relevance in diabetes. RESULTS Loss of b-cells identity impairs islet connectivity in Tg7 miceGenetic overexpression of miR-7 in b-cells results in diabetes from 4 weeks of age and is associated with decreased expression of mature b-cell differentiation markers, most notably INS1/2 and b-TFs genes ( Supplementary Figure 1). How dedifferentiation affects Ca 2+ dynamics and long-range b-cell:b-cell connectivity in diabetes remains unclear. To this end, we monitored intracellular free Ca 2+ dynamics in intact islets in response to elevated concentrations of glucose using a trappable intracellular Ca 2+ dye and multicellular imaging.Ca 2+ dynamics in response to 17 mM glucose were almost...

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Section: Smarca4/brg1 Is a Target Of Mir-7 In B-cellsmentioning

confidence: 79%

β-cell dedifferentiation is associated with epithelial-mesenchymal transition triggered by miR-7-mediated repression of mSwi/Snf complex

Mak

Ohlen

Wang

et al. 2019

Preprint

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“…Исследования структурных элементов стенок кишечника и поджелудочной железы проводятся в течение многих десятилетий, морфологическая диагностика осуществляется, как правило, гистологическими и гис тохимическими методами. В настоящее время для изу чения морфофункциональных особенностей клеток и тканей органов пищеварительной системы, а также их изменений при патологии используются методы иммуногистохимического выявления свойственных им белков [3][4][5]. Развитие большинства патологий в этих органах (исключая онкологию) связаны с двумя основными проблемами -нарушением иннервации и воспалительными процессами.…”

Section: Introductionunclassified

Immunohistochemical markers to study the digestive organs

Ei¹,

Петрова²,

Samedov³

et al. 2022

Clin. Exp. Morphology

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Introduction. To select an appropriate and informative histological method is a very important step in morphological analysis of the digestive organs, one of them being immunohistochemistry. The aim of this paper was to highlight the most effective immunohistochemical markers in addition to the well-known markers used in pathological diagnosis. Materials and methods. We studied sections of the intestine and pancreas of Wistar rats (n=20) and fragments of the human colon obtained during resection surgeries (n=4). We described and analyzed the results of immunohistochemical studies with neuronal and glial marker antibodies and inflammatory cells antibodies. Results. Neural (PGP 9.5 protein, tyrosine hydroxylase, synaptophysin, and serotonin) and glial markers (glial fibrillar acidic protein and S100 protein) enable for identifying all of the nervous structures in the murine digestive system such as neurons, nerve trunks and bundles, nerve plexuses, and terminals. Macrophage markers (CD68, Iba1) and mast cell marker (mast cell tryptase) can be applied to study the inflammatory process in the intestinal tissue. We described the key features of primary antibodies and fixative agents used in histopathology. Conclusion. We have shown that the described method is a promising assessment technique for histological studies of the intestine and pancreas pathologies. It can be used in diagnosing conditions associated with inflammation and neurodegeneration. Keywords: duodenum, colon, pancreas, rat, human, innervation, inflammation, immunohistochemistry

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Therapeutic effects of mesenchymal stem cell conditioned media on streptozotocin-induced diabetes in Wistar rats

Shalaby,

Abdel-Reheim,

Almanaa

et al. 2025

Regenerative Therapy

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Immunohistochemical detection of vimentin in pancreatic islet β- and α-cells of macrosomic infants of diabetic and nondiabetic mothers

Cited by 5 publications

References 34 publications

β-cell dedifferentiation is associated with epithelial-mesenchymal transition triggered by miR-7-mediated repression of mSwi/Snf complex

β-cell dedifferentiation is associated with epithelial-mesenchymal transition triggered by miR-7-mediated repression of mSwi/Snf complex

Immunohistochemical markers to study the digestive organs

Therapeutic effects of mesenchymal stem cell conditioned media on streptozotocin-induced diabetes in Wistar rats

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