WISP1, a Pro-mitogenic, Pro-survival Factor, Mediates Tumor Necrosis Factor-α (TNF-α)-stimulated Cardiac Fibroblast Proliferation but Inhibits TNF-α-induced Cardiomyocyte Death

Venkatachalam, Karthikeyan; Venkatesan, Balachandar; Valente, Anthony J.; Melby, Peter C.; Nandish, Sailesh; Reusch, Jane E.B.; Clark, Robert A.; Chandrasekar, Bysani

doi:10.1074/jbc.m809757200

Cited by 104 publications

(114 citation statements)

References 64 publications

(66 reference statements)

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“…43296; Active Motif, Carlsbad, CA) (30,39). Activation of NF-B was also confirmed by reporter assays using adenoviral transduction of an NF-B reporter vector (Ad.NF-B-Luc, MOI 50) (38).…”

Section: Methodsmentioning

confidence: 99%

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Interleukin-18 induces EMMPRIN expression in primary cardiomyocytes via JNK/Sp1 signaling and MMP-9 in part via EMMPRIN and through AP-1 and NF-κB activation

Reddy

Prabhu²,

Mummidi

et al. 2010

American Journal of Physiology-Heart and Circulatory Physiology

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and the extracellular matrix metalloproteinase (MMP) inducer (EMMPRIN) stimulate the expression of proinflammatory cytokines and MMPs and are elevated in myocardial hypertrophy, remodeling, and failure. Here, we report several novel findings in primary cardiomyocytes treated with IL-18. First, IL-18 activated multiple transcription factors, including NF-B (p50 and p65), activator protein (AP)-1 (cFos, cJun, and JunD), GATA, CCAAT/enhancer-binding protein, myocyte-specific enhancerbinding factor, interferon regulatory factor-1, p53, and specific protein (Sp)-1. Second, IL-18 induced EMMPRIN expression via myeloid differentiation primary response gene 88/IL-1 receptor-associated kinase/TNF receptor-associated factor-6/JNK-dependent Sp1 activation. Third, IL-18 induced a number of MMP genes, particularly MMP-9, at a rapid rate as well as tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-3 at a slower rate. Finally, the IL-18 induction of MMP-9 was mediated in part via EMMPRIN and through JNK-and ERK-dependent AP-1 activation and p38 MAPK-dependent NF-B activation. These results suggest that the elevated expression of IL-18 during myocardial injury and inflammation may favor EMMPRIN and MMP induction and extracellular matrix degradation. Therefore, targeting IL-18 or its signaling pathways may be of potential therapeutic benefit in adverse remodeling. myocardial remodeling; extracellular matrix; extracellular matrix metalloproteinase inducer; matrix metalloproteinase; tissue inhibitor of metalloproteinase; c-Jun NH2 terminal kinase; specific protein-1; activator protein-1; nuclear factor-B

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“…43296; Active Motif, Carlsbad, CA) (30,39). Activation of NF-B was also confirmed by reporter assays using adenoviral transduction of an NF-B reporter vector (Ad.NF-B-Luc, MOI 50) (38).…”

Section: Methodsmentioning

confidence: 99%

“…Binding of Sp1 to the EMMPRIN 5=-cis regulatory region in vivo was determined by chromatin immunoprecipitation (ChIP) assay. ACMs were treated with IL-18 (5 ng/ml for 2 h), and the ChIP assay carried out as previously described (7,39). Immunocomplexes were prepared using anti-Sp1 antibody (sc-14027 X, Santa Cruz Biotechnology,).…”

Section: Methodsmentioning

confidence: 99%

Interleukin-18 induces EMMPRIN expression in primary cardiomyocytes via JNK/Sp1 signaling and MMP-9 in part via EMMPRIN and through AP-1 and NF-κB activation

Reddy

Prabhu²,

Mummidi

et al. 2010

American Journal of Physiology-Heart and Circulatory Physiology

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“…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%

“…Among the significantly upregulated genes, WNT-inducible secreted protein 1 (Wisp1/CCN4), whose expression was upregulated 3.7-fold by Bmp3 (Fig. 1A), was of particular interest, because it has been previously shown to promote proliferation of cardiac fibroblasts (Venkatachalam et al 2009), lung epithelial cells (Königshoff et al 2009) and osteogenic cells (Inkson et al 2009). Consequently, we selected Wisp1 as a potential candidate gene and verified the magnitude of the increase in levels of Wisp1 mRNA following Bmp3 treatment with qRT-PCR ( Fig.…”

Section: Effects Of Bmp3 On Msc Transcriptomementioning

confidence: 99%

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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“…These domains determine the function of CCN member proteins during development and in human diseases. Although Wisp1 has been linked to oncogenic transformation (Pennica et al 1998;Xu et al 2000), proliferation and cell survival (Venkatachalam et al 2009;Venkatesan et al 2010), and epithelial-to-mesenchymal transition (Konigshoff et al 2009), little is known about its downstream genes or how it regulates their expression. In this study, we identified several downstream ECM components that were regulated by Wisp1, likely through its interaction with biglycan.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-mediated regulation of extracellular matrix formation modulates somatic cell reprogramming

Dang

Chang

et al. 2014

RNA

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Somatic cells can be reprogrammed to reach an embryonic stem cell-like state by overexpression of defined factors. Recent studies have greatly improved the efficiency of the reprogramming process but the underlying mechanisms regulating the transition from a somatic to a pluripotent state are still relatively unknown. MicroRNAs (miRs) are small noncoding RNAs that primarily regulate target gene expression post-transcriptionally. Here we present a systematic and comprehensive study of microRNAs in mouse embryonic fibroblasts (MEFs) during the early stage of cell fate decisions and reprogramming to a pluripotent state, in which significant transcriptional and epigenetic changes occur. One microRNA found to be highly induced during this stage of reprogramming, miR-135b, targeted the expression of extracellular matrix (ECM) genes including Wisp1 and Igfbp5. Wisp1 was shown to be a key regulator of additional ECM genes that serve as barriers to reprogramming. Regulation of Wisp 1 is likely mediated through biglycan, a glycoprotein highly expressed in MEFs that is silenced in reprogrammed cells. Collectively, this report reveals a novel link between microRNA-mediated regulation of ECM formation and somatic cell reprogramming, and demonstrates that microRNAs are powerful tools to dissect the intracellular and extracellular molecular mechanisms of reprogramming.

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WISP1, a Pro-mitogenic, Pro-survival Factor, Mediates Tumor Necrosis Factor-α (TNF-α)-stimulated Cardiac Fibroblast Proliferation but Inhibits TNF-α-induced Cardiomyocyte Death

Cited by 104 publications

References 64 publications

Interleukin-18 induces EMMPRIN expression in primary cardiomyocytes via JNK/Sp1 signaling and MMP-9 in part via EMMPRIN and through AP-1 and NF-κB activation

Interleukin-18 induces EMMPRIN expression in primary cardiomyocytes via JNK/Sp1 signaling and MMP-9 in part via EMMPRIN and through AP-1 and NF-κB activation

Wisp1 mediates Bmp3-stimulated mesenchymal stem cell proliferation

MicroRNA-mediated regulation of extracellular matrix formation modulates somatic cell reprogramming

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