WISP 1 is an important survival factor in human mesenchymal stromal cells

Schlegelmilch, Katrin; Keller, Alexander; Zehe, Viola; Hondke, Sylvia; Schilling, Tatjana; Jakob, Franz; Klein-Hitpaß, Ludger; Schütze, Norbert

doi:10.1016/j.gene.2014.09.002

Cited by 18 publications

(20 citation statements)

References 46 publications

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“…In the present study, we demonstrate that i) Bmp3 induces dynamic changes in C3H10T1/2 MSC transcriptome, including a significant increase in the expression of Wisp1, a key pro-survival factor previously identified in non-adipose cells (Venkatachalam et al 2009, Schlegelmilch et al 2014; ii) Bmp3-induced upregulation of Wisp1 expression proceeds Bmp3-stimulated MSC proliferation; iii) recombinant Wisp1 potently stimulates MSC proliferation; and iv) siRNA-mediated knockdown of Wisp1 expression significantly attenuates the stimulatory effect of Bmp3 on MSC proliferation. Taken together, these findings reveal Wisp1 as a novel target of Bmp3, and demonstrate that the Bmp3/Wisp1 signaling pathway plays an important role in MSC proliferation.…”

Section: Discussionsupporting

confidence: 58%

“…Wisp1 is also a pro-survival factor, because it stimulates proliferation of several non-adipose cell types, including cardiac fibroblasts (Venkatachalam et al 2009), lung epithelial cells (Königshoff et al 2009), osteogenic cells (Inkson et al 2009). Furthermore, reduced expression of Wisp1 is associated with enhanced apoptosis in cultured human mesenchymal stromal cells (Schlegelmilch et al 2014). Therefore, we chose Wisp1 as a candidate gene for this study.…”

Section: Discussionmentioning

confidence: 99%

“…Given that Wisp1 was upregulated following Bmp3 treatment and is a known pro-survival factor in various nonadipose cell types (Inkson et al 2009, Königshoff et al 2009, Venkatachalam et al 2009, Schlegelmilch et al 2014, coupled with previous findings that human adipocyte differentiation was associated with elevated Wisp1 expression (Murahovschi et al 2015), we examined the involvement of Wisp1 in mediating Bmp3-induced MSC proliferation. We first determined if Bmp3-induced upregulation of Wisp1 expression preceded Bmp3-stimulated cell proliferation by conducting a time-dependent experiment.…”

Section: Effects Of Bmp3 On Wisp1 Expression and Msc Proliferationmentioning

confidence: 99%

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Wisp1 mediates Bmp3-stimulated mesenchymal stem cell proliferation

Cernea¹,

Tang²,

Guan³

et al. 2015

Journal of Molecular Endocrinology

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Adipose tissue expansion, resulting from adipocyte hyperplasia and/or hypertrophy, is a hallmark of obesity. Adipocytes are derived from mesenchymal stem cells (MSCs) through adipogenesis, a process involving three key steps: proliferation, commitment and differentiation. Although studies have elaborated on the mechanisms regulating adipocyte commitment and differentiation, the factors that control MSC proliferation remain largely unknown. Previously, we demonstrated that bone morphogenetic protein 3 (Bmp3), the expression of which was upregulated in our rat model of hyperplasic visceral adiposity, potently stimulated MSC proliferation. In the present study, we investigate the molecular target of Bmp3. We conducted DNA microarray analysis on MSCs treated with and without Bmp3 and identified WNT1-inducible signaling pathway protein 1 (Wisp1) as a differentially expressed gene, whose expression was upregulated 3.7-fold by Bmp3. Wisp1 is a proliferative agent in various non-adipose cell types and is implicated in adipogenesis. Therefore, we tested the hypothesis that Wisp1 mediates Bmp3 stimulation of MSC proliferation. We showed that Bmp3 increased the expression of Wisp1 as early as 3 h following Bmp3 treatment in MSCs. Importantly, the upregulated Wisp1 expression preceded Bmp3-induced MSC proliferation, as determined by [ 3 H]-thymidine incorporation.Furthermore, treatment of MSCs with recombinant Wisp1 led to a concentration-dependent increase in [ 3 H]-thymidine incorporation with a maximal increase of 300%. In addition, siRNA-mediated knockdown of Wisp1 expression attenuated Bmp3-induced MSC proliferation. Taken together, our present findings reveal Wisp1 as a novel target of Bmp3 and suggest that the Bmp3/Wisp1 signaling pathway play a key role in MSC proliferation, and consequently adipogenesis.

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Section: Discussionsupporting

confidence: 58%

Section: Discussionmentioning

confidence: 99%

Section: Effects Of Bmp3 On Wisp1 Expression and Msc Proliferationmentioning

confidence: 99%

See 1 more Smart Citation

Wisp1 mediates Bmp3-stimulated mesenchymal stem cell proliferation

Cernea¹,

Tang²,

Guan³

et al. 2015

Journal of Molecular Endocrinology

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“…The WNT1 inducible signaling pathway (WISP) proteins WISP1/CCN4 and WISP2/CCN5 are downstream in the WNT1 signaling pathway and are also relevant to malignant transformation, cancer cell surviving, invasion and motility [12][13][14]. Furthermore, the elevated levels of WISP1/CCN4 and CYR61/CCN1 in primary breast cancers were associated with more advanced features [15].…”

mentioning

confidence: 99%

Effect of hypoxia on the expression of genes that encode some IGFBP and CCN proteins in U87 glioma cells depends on IRE1 signaling

Minchenko¹,

Kharkova²,

Minchenko³

et al. 2015

Ukr.Biochem.J.

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Insulin-like growth factor binding proteins (IGFBPs ) contain insulin-like growth factor (IGF) binding domain and play an important role in the regulation of numerous metabolic and proliferative processes mainly through interaction with IGF1 and IGF2, their cell surface receptors as well as insulin receptor, alter the half-life of the IGFs, modifying their biological activity. It is well known that insulin-like growth factors and the signal transduction networks play important roles in tumorigenesis and metastasis as well as in metabolic diseases [1,2]. IGFBPs participate in endoplasmic reticulum stress, which is an important factor of tumor growth, insulin resistance, and obesity [3][4][5]. It is interesting to note that there is the cross talk between IGF and insulin receptor signaling pathways at the receptor level or at downstream signaling level. This cross talk significantly changed a variety of cancers as a result of insulin receptor isoform. A formation of hybrid receptor isoforms between receptors for IGF1 and insulin, which are sensitive to the stimulation of all three IGF axis ligands, as well as hybrid receptors of IGF1/insulin receptor with other tyrosine kinase potentiate the transformation of cells, tumorigenesis, and tumor neovascularization [6].The IGFBPs have different affinity for insulin-like growth factors. They bind and regulate the availability of both insulin-like growth factors and inhibit or stimulate the growth promoting effects of the IGFs through IGF/INS receptors and through other signaling pathways and regulate cell proliferation and survival as well as angiogenesis and cancer експериментальні роботи doi: http://dx

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“…Computation and pairwise comparison of the obtained signals were performed according to a previously described protocol. 18 In brief, statistical analyses of the regulated probe sets were performed with the statistics software R 19 and its additional component for microarray analyses, Bioconductor. 20 To analyze the Affymetrix GeneChip®, the analysis add-on package Affy was used.…”

Section: Microarray and Gene Ontology Analysesmentioning

confidence: 99%

Physical contact between mesenchymal stem cells and endothelial precursors induces distinct signatures with relevance to the very early phase of regeneration

Hafen

Wiesner

Schlegelmilch

et al. 2018

J of Cellular Biochemistry

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Multipotent adult stem cells/precursor cells, especially of the mesenchymal and endothelial lineage, may have great potential for bone tissue engineering. Although their potential is highly recognized, not much is known about the underlying molecular mechanisms that initiate the regeneration process, connect osteogenesis, and angiogenesis and, finally, orchestrate renewal of bone tissue. Our study addressed these questions by generating two in vitro cell culture models to examine the changes in the global gene expression patterns of endothelial precursor cells and mesenchymal stem cells after 24 hours of either humoral (conditioned medium) or direct cell-cell interaction (co-culture). Endothelial precursor cells were isolated from human buffy coat and mesenchymal stem cells from the bone marrow of the femoral head. The comparison of the treated and control cells by microarray analyses revealed in total more than 1500 regulated genes, which were analyzed for their affiliation to angiogenesis and osteogenesis. Expression array analyses at the RNA and protein level revealed data with respect to regulated genes, pathways and targets that may represent a valid basis for further dissection of the systems biology of regeneration processes. It may also be helpful for the reconstitution of the natural composition of a regenerative microenvironment when targeting tissue regeneration both in vitro and in situ.

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WISP 1 is an important survival factor in human mesenchymal stromal cells

Cited by 18 publications

References 46 publications

Wisp1 mediates Bmp3-stimulated mesenchymal stem cell proliferation

Wisp1 mediates Bmp3-stimulated mesenchymal stem cell proliferation

Effect of hypoxia on the expression of genes that encode some IGFBP and CCN proteins in U87 glioma cells depends on IRE1 signaling

Physical contact between mesenchymal stem cells and endothelial precursors induces distinct signatures with relevance to the very early phase of regeneration

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