Identification of novel targets of diabetic nephropathy and PEDF peptide treatment using RNA-seq

Rubin, Ana; Salzberg, Anna C.; Imamura, Yuka; Grivitishvilli, Anzor; Tombran-Tink, Joyce

doi:10.1186/s12864-016-3199-8

Cited by 32 publications

(20 citation statements)

References 49 publications

(63 reference statements)

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“…We also found that the absence of Mcpt6 was associated with elevated expression of the micro RNA miR3098. Interestingly, miR3098 has previously been implicated in lung cancer (Wang, Xu, & Wang, ) and diabetes (Rubin, Salzberg, Imamura, Grivitishvilli, & Tombran‐Tink, ), although the exact role miR3098 under these conditions has not been clarified.…”

Section: Discussionmentioning

confidence: 99%

Protective role of mouse mast cell tryptase Mcpt6 in melanoma

Grujić

Hellman

Gustafson

et al. 2020

Pigment Cell Melanoma Res

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Tryptase‐positive mast cells populate melanomas, but it is not known whether tryptase impacts on melanoma progression. Here we addressed this and show that melanoma growth is significantly higher in tryptase‐deficient (Mcpt6−/−) versus wild‐type mice. Histochemical analysis showed that mast cells were frequent in the tumor stroma of both wild‐type and Mcpt6−/− mice, and also revealed their presence within the tumor parenchyma. Confocal microscopy analysis revealed that tryptase was taken up by the tumor cells. Further, tryptase‐positive granules were released from mast cells and were widely distributed within the tumor tissue, suggesting that tryptase could impact on the tumor microenvironment. Indeed, gene expression analysis showed that the absence of Mcpt6 caused decreased expression of numerous genes, including Cxcl9, Tgtp2, and Gbp10, while the expression of 5p‐miR3098 was enhanced. The levels of CXCL9 were lower in serum from Mcpt6−/− versus wild‐type mice. In further support of a functional impact of tryptase on melanoma, recombinant tryptase (Mcpt6) was taken up by cultured melanoma cells and caused reduced proliferation. Altogether, our results indicate a protective role of mast cell tryptase in melanoma growth.

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Section: Discussionmentioning

confidence: 99%

Protective role of mouse mast cell tryptase Mcpt6 in melanoma

Grujić

Hellman

Gustafson

et al. 2020

Pigment Cell Melanoma Res

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“…In addition, the relationship between lncRNA-AI838599 and kidney is also reported previously. GSE87899 (GEO DataSets) [33] showed increased lncRNA-AI838599 expression in the kidney of D2.B6-Ins2 Akita /MatbJ DN mouse model compared to the wild type. e similar expression trend of lncRNA-AI838599 was also seen in miR-25 knockdown mice that show similar phenotypes of DN such as proteinuria, extracellular matrix accumulation, and podocyte foot process effacement [34].…”

Section: Discussionmentioning

confidence: 99%

Altered Expression of Long Noncoding and Messenger RNAs in Diabetic Nephropathy following Treatment with Rosiglitazone

Zhang

Zhou

et al. 2020

BioMed Research International

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Diabetic nephropathy (DN) is characterized by metabolic disorder and inflammation. However, the regulatory effects that long noncoding RNAs (lncRNAs) have on the pathogenesis of DN and on the efficacy of rosiglitazone treatment have yet to be clearly defined. Herein, we performed unbiased RNA sequencing to characterize the transcriptomic profiles in db/db diabetic mouse model with or without rosiglitazone treatment that served to improve the phenotypes of DN. Moreover, RNA-seq profiling revealed that the development of DN caused an upregulation in the expression of 1176 mRNAs and a downregulation in the expression of 1010 mRNAs compared to controls, with the expression of 251 mRNAs being returned to normal following treatment with rosiglitazone. Further, 88 upregulated and 68 downregulated lncRNAs were identified in db/db mice compared to controls, 10 of which had their normal expression restored following treatment with rosiglitazone. Bioinformatic analysis revealed that the primary pathways involved in the pathogenesis of DN, and subsequently in the therapeutic effects of PPARc, are related to inflammatory and metabolic processes. From bioinformatics analysis, lncRNA-AI838599 emerged as a novel molecular mechanism for rosiglitazone treatment in DN through TNFα-NFκb pathway. ese findings may indicate a new molecular regulatory approach for the development of DN therapeutic agents.

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“…The gene expression data were provided as supplementary material. The heat map of gene differentiation was generated using the method described by Rubin et al [ 21 ]. Briefly, a heat map of the median-centered FPKM (fragments per kilobase of exon per million fragments mapped) values corresponding to the transcripts in samples was generated using the heatmap.2 function of the gplots R package.…”

Section: Methodsmentioning

confidence: 99%

Autophagy Is Indispensable for the Self‐Renewal and Quiescence of Ovarian Cancer Spheroid Cells with Stem Cell‐Like Properties

Wang

Xin

et al. 2018

Oxidative Medicine and Cellular Longevity

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Epithelial ovarian cancer has the highest mortality rate of all gynecologic cancers. Cancer stem cells are considered to be the initiating cells of tumors. It is known that spheroid culture promotes ovarian cancer cells to acquire stem cell characteristics and to become stem cell-like. But the mechanisms remain largely unclear. Our data show that autophagy is sustainably activated in ovarian cancer spheroid cells. Inhibition of autophagy by knockdown of ATG5 abolishes the self-renewal ability of ovarian cancer spheroid cells. Knockdown of ATG5 prevents ovarian cancer spheroid cells to enter quiescent state. Autophagy is critical for quiescent ovarian cancer spheroid cells to reenter the cell cycle because rapamycin can promote quiescent ovarian cancer spheroid cells to form colonies on soft agar and knockdown of ATG5 can arrest ovarian cancer cells in G0/G1. Autophagy and NRF2 form a positive feedback regulation loop to regulate reactive oxygen species (ROS) levels in ovarian cancer spheroid cells. The optimal ROS level, neither too high nor too low, facilitates the self-renewal marker, NOTCH1, to reach to the highest level. Bafilomycin A1 can impair the self-renewal of ovarian cancer spheroid cells by disturbing ROS levels.

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Identification of novel targets of diabetic nephropathy and PEDF peptide treatment using RNA-seq

Cited by 32 publications

References 49 publications

Protective role of mouse mast cell tryptase Mcpt6 in melanoma

Protective role of mouse mast cell tryptase Mcpt6 in melanoma

Altered Expression of Long Noncoding and Messenger RNAs in Diabetic Nephropathy following Treatment with Rosiglitazone

Autophagy Is Indispensable for the Self‐Renewal and Quiescence of Ovarian Cancer Spheroid Cells with Stem Cell‐Like Properties

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