Regulator of G-Protein Signaling-5 Is a Marker of Hepatic Stellate Cells and Expression Mediates Response to Liver Injury

Bahrami, Arya J.; Gunaje, Jagadambika J.; Hayes, Brian; Riehle, Kimberly J.; Kenerson, Heidi L.; Yeung, Raymond S.; Stempien-Otero, April S.; Campbell, Jean S.; Mahoney, William M.

doi:10.1371/journal.pone.0108505

Cited by 19 publications

(16 citation statements)

References 82 publications

(91 reference statements)

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“…Our data further indicate that loss of RGS5 in pericytes does not directly affect type I collagen and fibronectin production after stroke, as the overall deposition of these ECM proteins was not changed. This suggests that the described role of RGS5 in ECM production in other organs might not be applicable to brain pericytes after stroke (Bahrami et al, ; Holobotovskyy et al, ; Li et al, ). RGS proteins are conserved, and the fact that that loss of RGS5 does not directly affect type I collagen and fibronectin could be due to compensatory upregulation of other RGS proteins (Ganss, ).…”

Section: Discussionmentioning

confidence: 99%

Parenchymal pericytes are not the major contributor of extracellular matrix in the fibrotic scar after stroke in male mice

Roth

Enström

Aghabeick

et al. 2019

J of Neuroscience Research

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Scar formation after injury of the brain or spinal cord is a common event. While glial scar formation by astrocytes has been extensively studied, much less is known about the fibrotic scar, in particular after stroke. Platelet‐derived growth factor receptor ß‐expressing (PDGFRß+) pericytes have been suggested as a source of the fibrotic scar depositing fibrous extracellular matrix (ECM) proteins after detaching from the vessel wall. However, to what extent these parenchymal PDGFRß+ cells contribute to the fibrotic scar and whether targeting these cells affects fibrotic scar formation in stroke is still unclear. Here, we utilize male transgenic mice that after a permanent middle cerebral artery occlusion stroke model have a shift from a parenchymal to a perivascular location of PDGFRß+ cells due to the loss of regulator of G‐protein signaling 5 in pericytes. We find that only a small fraction of parenchymal PDGFRß+ cells co‐label with type I collagen and fibronectin. Consequently, a reduction in parenchymal PDGFRß+ cells by ca. 50% did not affect the overall type I collagen or fibronectin deposition after stroke. The redistribution of PDGFRß+ cells to a perivascular location, however, resulted in a reduced thickening of the vascular basement membrane and changed the temporal dynamics of glial scar maturation after stroke. We demonstrate that parenchymal PDGFRß+ cells are not the main contributor to the fibrotic ECM, and therefore targeting these cells might not impact on fibrotic scar formation after stroke.

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Section: Discussionmentioning

confidence: 99%

Parenchymal pericytes are not the major contributor of extracellular matrix in the fibrotic scar after stroke in male mice

Roth

Enström

Aghabeick

et al. 2019

J of Neuroscience Research

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“…On the other hand, for liver advantage transcripts, in region c, MMD (monocyte to macrophage differentiation-associated protein) indicated expansion of Kupffer cells (KCs) in liver55. In region f, IL-17C suggested promotion of Th17 response56; RGS5b (regulator of G-protein signaling 5b) indicated roles of hepatic satellite cells upon inflammation57. In addition, C1q in regions f and g could facilitate complement activation and phagocytosis58.…”

Section: Discussionmentioning

confidence: 99%

Fish gut-liver immunity during homeostasis or inflammation revealed by integrative transcriptome and proteome studies

Song

Wang

et al. 2016

Sci Rep

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The gut-associated lymphoid tissue, connected with liver via bile and blood, constructs a local immune environment of both defense and tolerance. The gut-liver immunity has been well-studied in mammals, yet in fish remains largely unknown, even though enteritis as well as liver and gallbladder syndrome emerged as a limitation in aquaculture. In this study, we performed integrative bioinformatic analysis for both transcriptomic (gut and liver) and proteomic (intestinal mucus and bile) data, in both healthy and infected tilapias. We found more categories of immune transcripts in gut than liver, as well as more adaptive immune in gut meanwhile more innate in liver. Interestingly reduced differential immune transcripts between gut and liver upon inflammation were also revealed. In addition, more immune proteins in bile than intestinal mucus were identified. And bile probably providing immune effectors to intestinal mucus upon inflammation was deduced. Specifically, many key immune transcripts in gut or liver as well as key immune proteins in mucus or bile were demonstrated. Accordingly, we proposed a hypothesized profile of fish gut-liver immunity, during either homeostasis or inflammation. Current data suggested that fish gut and liver may collaborate immunologically while keep homeostasis using own strategies, including potential unique mechanisms.

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“…We provide evidence that MuSCs from this mouse model have tumorigenic potential and are capable of forming tumorspheres in vitro and solid tumors in vivo when transplanted into immunodeficient mice, indicating that RMS in dystrophic contexts can originate from MuSCs. Finally, we show that Ccl11 and Rgs5, two genes involved in the inflammatory response and stem cell fate decisions during wound healing (Bahrami et al, 2014; Kindstedt et al, 2017; Rees et al, 2015), are downregulated in MuSCs from mdx/mTR mice lacking p53, and their overexpression leads to decreased tumorsphere size. Together, these findings demonstrate that MuSCs can give rise to RMS in high-turnover conditions, highlighting the importance of assessing MuSC behavior after treatments aimed at increasing their self-renewal ability for treating DMD.…”

Section: Introductionmentioning

confidence: 81%

Muscle Stem Cells Give Rise to Rhabdomyosarcomas in a Severe Mouse Model of Duchenne Muscular Dystrophy

2019

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SUMMARY Most human cancers originate from high-turnover tissues, while low-proliferating tissues, like skeletal muscle, exhibit a lower incidence of tumor development. In Duchenne muscular dystrophy (DMD), which induces increased skeletal muscle regeneration, tumor incidence is increased. Rhabdomyosarcomas (RMSs), a rare and aggressive type of soft tissue sarcoma, can develop in this context, but the impact of DMD severity on RMS development and its cell of origin are poorly understood. Here, we show that RMS latency is affected by DMD severity and that muscle stem cells (MuSCs) can give rise to RMS in dystrophic mice. We report that even before tumor formation, MuSCs exhibit increased self-renewal and an expression signature associated with RMSs. These cells can form tumorspheres in vitro and give rise to RMSs in vivo. Finally, we show that the inflammatory genes Ccl11 and Rgs5 are involved in RMS growth. Together, our results show that DMD severity drives MuSC-mediated RMS development.

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Regulator of G-Protein Signaling-5 Is a Marker of Hepatic Stellate Cells and Expression Mediates Response to Liver Injury

Cited by 19 publications

References 82 publications

Parenchymal pericytes are not the major contributor of extracellular matrix in the fibrotic scar after stroke in male mice

Parenchymal pericytes are not the major contributor of extracellular matrix in the fibrotic scar after stroke in male mice

Fish gut-liver immunity during homeostasis or inflammation revealed by integrative transcriptome and proteome studies

Muscle Stem Cells Give Rise to Rhabdomyosarcomas in a Severe Mouse Model of Duchenne Muscular Dystrophy

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