A Transcriptional Sequencing Analysis of Islet Stellate Cell and Pancreatic Stellate Cell

Wang, Xiaohang; Li, Wei; Chen, Juan; Zhao, Sheng; Qiu, Shanhu; Yin, Han; Carvalho, Vladmir; Zhou, Yunting; Shi, Ruifeng; Hu, Jiannan; Li, Shenyi; Nijiati, Munire; Sun, Zilin

doi:10.1155/2018/7361684

Cited by 11 publications

(9 citation statements)

References 28 publications

(18 reference statements)

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“…We previously found that ISCs are responsible for islet fibrosis ( 14 ). However, we also demonstrated that ISCs and PSCs are similar but not identical via transcriptome sequencing ( 17 ). Compared with PSCs, ISCs exhibit lower proliferation and migration rates, are more easily to be activated by stimulators, and have fewer lipid droplets.…”

Section: Discussionmentioning

confidence: 81%

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Screening and Identification of Key Genes for Activation of Islet Stellate Cell

et al. 2021

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BackgroundIt has been demonstrated that activated islet stellate cells (ISCs) play a critical role in islet fibrogenesis and significantly contribute to the progression of type 2 diabetes mellitus. However, the key molecules responsible for ISCs activation have not yet been determined. This study aimed to identify the potential key genes involved in diabetes-induced activation of ISCs.MethodStellate cells were isolated from three 10-week-old healthy male Wistar rats and three Goto-Kakizaki (GK) rats. Cells from each rat were primary cultured under the same condition. A Genome-wide transcriptional sequence of stellate cells was generated using the Hiseq3000 platform. The identified differentially expressed genes were validated using quantitative real-time PCR and western blotting in GK rats, high fat diet (HFD) rats, and their controls.ResultsA total of 204 differentially expressed genes (DEGs) between GK. ISCs and Wistar ISCs (W.ISCs) were identified, accounting for 0.58% of all the 35,362 genes detected. After the Gene Ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analyses, the mRNA levels of these genes were further confirmed by real-time PCR in cultured ISCs. We then selected Fos, Pdpn, Bad as the potential key genes for diabetes-induced activation of ISCs. Finally, we confirmed the protein expression levels of FOS, podoplanin, and Bad by western blotting and immunofluorescence in GK rats, HFD rats, and their controls. The results showed that the expression level of FOS was significantly decreased, while podoplanin and Bad were significantly increased in GK.ISCs and HFD rats compared with controls, which were consistent with the expression of α-smooth muscle actin.ConclusionsA total of 204 DEGs were found between the GK.ISCs and W.ISCs. After validating the expression of potential key genes from GK rats and HFD rats, Fos, Pdpn, and Bad might be potential key genes involved in diabetes-induced activation of ISCs.

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Section: Discussionmentioning

confidence: 81%

“…However, they exhibit differences in cell activation, proliferation, migration, and collagen synthesis. Through transcriptome sequencing, we also found that ISCs and PSCs have similar characteristics ( 17 ). Stellate cells stay quiescent in general.…”

Section: Introductionmentioning

confidence: 85%

Screening and Identification of Key Genes for Activation of Islet Stellate Cell

et al. 2021

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“…We found that insulin secretion from islets cocultured in vitro with db/m mouse ISCs was significantly increased compared to that from islets cocultured with ISCs from db/db mice. Subsequent iTRAQ protein screening of the ISCs showed that both ISCs cultured under static conditions and their supernatants showed high Wnt5a protein expression compared with diabetic ISCs [24][25][26][27][28][29][30]. e mechanisms leading to ISCs quiescence play an important role in regulating islet function via the Wnt5a-Fzd5 system and can help us understand the crosstalk between cells inside the islets of Langerhans and serve as a target for the prevention of diabetes.…”

Section: Discussionmentioning

confidence: 99%

Islet Stellate Cells Regulate Insulin Secretion via Wnt5a in Min6 Cells

Jones

Geng

et al. 2020

International Journal of Endocrinology

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Background. Type 2 diabetes mellitus is a serious public health problem worldwide. Accumulating evidence has shown that β-cell dysfunction is an important mechanism underlying diabetes mellitus. e changes in the physiological state of islet stellate cells (ISCs) and the effects of these cells on β cell function play an important role in the development of diabetes. is study aimed at elucidating the mechanism by which ISCs regulate insulin secretion from Min6 cells via the Wnt5a protein. Methods. Glucosestimulated insulin secretion (GSIS) from Min6 cells was examined by estimating the insulin levels in response to high glucose challenge after culture with ISC supernatant or exogenous Wnt5a. Western blotting and quantitative real-time polymerase chain reaction (qRT-PCR) analyses were used to observe changes in the β-catenin, receptor tyrosine kinase-like orphan receptor 2 (Ror2), Ca (2+)/calmodulin (CaM)-dependent protein kinase II (CamKII), forkhead box O1 (FoxO1), pancreatic and duodenal homeobox 1 (PDX1), glucose transporter 2 (Glut2), insulin, and Cask mRNA and protein levels in the Wnt and insulin secretory pathways. Flow cytometry was used to confirm the intracellular Ca 2+ concentration in Min6 cells. Results. We observed a significant increase in insulin secretion from Min6 cells cocultured in vitro with supernatant from db/m mouse ISCs compared to that from Min6 cells cocultured with supernatant from db/db mouse ISCs; e intracellular Ca 2+ concentration in Min6 cells increased in cultured in vitro with supernatant from db/m mouse ISCs and exogenous Wnt5a compared to that from control Min6 cells. Culture of Min6 cells with exogenous Wnt5a caused a significant increase in pCamKII, pFoxO1, PDX-1, and Glut2 levels compared to those in Min6 cells cultured alone; this treatment further decreased Ror2 and Cask expression but did not affect β-catenin expression. Conclusion. ISCs regulate insulin secretion from Min6 cells through the Wnt5a protein-induced Wntcalcium and FoxO1-PDX1-GLUT2-insulin signalling cascades.

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“…In pervious study, our group has compared the biological characteristics of ISCs with typical PSCs, and found that there are 32 significant differentially expressed genes between activated PSCs and activated ISCs. Due to fewer lipid droplets, ISCs appeared to be more easily activated by stimulators, and demonstrated reduced proliferation and migration abilities [34]. Therefore, the biological phenotypes of ISCs and PSCs are similar, but not completely identical.…”

Section: Discussionmentioning

confidence: 99%

Vitamin A deficiency causes islet dysfunction by inducing islet stellate cell activation via cellular retinol binding protein 1

Zhou

Sun

et al. 2020

Int. J. Biol. Sci.

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Background: Vitamin A (VA) plays an essential role in pancreatic homeostasis. Islet stellate cells (ISCs) are VA-storing cells in pancreatic islets. Herein, we have investigated the effect of VA on glucose homeostasis trough regulation of ISCs function in dietary VA deficiency model mice. Methods: Male C57BL/6 mice were randomly fed a VA-sufficient, a VA-deficient (VAD) or a VAD-rescued diet. Glucose metabolism was assessed by glucose tolerance tests and immunohistochemistry. ISCs activation degree was evaluated by immunofluorescence, quantitative PCR and western blotting in both, retinol-treated cultured ISCs and model mice. Changes in ISCs phenotype and their effect on islets were assessed by lentiviral transduction and enzyme-linked immunosorbent assays in a co-culture system. Results: VAD mice showed irregular shaped islet, glucose intolerance, islet size distribution excursions, and upregulated expression of α-smooth muscle actin (α-SMA, marker of ISCs activation). Reintroduction of dietary VA restored pancreatic VA levels, endocrine hormone profiles, and inhibited ISCs activation. Incubation with retinol increased the expression of VA signaling factors in ISCs, including cellular retinol binding protein 1 (CRBP1). The knockdown of CRBP1 maintained the quiescent ISCs phenotype and reduced the damage of activated ISCs on islet function. Conclusions: VA deficiency reduced islet function by activating ISCs in VAD mice. Restoring ISCs quiescence via CRBP1 inhibition could reverse the impairment of islet function caused by activated ISCs exposure.

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A Transcriptional Sequencing Analysis of Islet Stellate Cell and Pancreatic Stellate Cell

Cited by 11 publications

References 28 publications

Screening and Identification of Key Genes for Activation of Islet Stellate Cell

Screening and Identification of Key Genes for Activation of Islet Stellate Cell

Islet Stellate Cells Regulate Insulin Secretion via Wnt5a in Min6 Cells

Vitamin A deficiency causes islet dysfunction by inducing islet stellate cell activation via cellular retinol binding protein 1

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