Complement factor 5 is a quantitative trait gene that modifies liver fibrogenesis in mice and humans

Hillebrandt, S.; Wasmuth, Hermann E.; Weiskirchen, Ralf; Hellerbrand, Claus; Keppeler, Hildegard; Werth, Alexa; Schirin-Sokhan, Ramin; Wilkens, Gabriele; Geier, Andreas; Lorenzen, Johann; Köhl, Jörg; Gressner, A. M.; Matern, Siegfried; Lammert, Frank

doi:10.1038/ng1599

Cited by 241 publications

(206 citation statements)

References 47 publications

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“…Inbred mouse strain genomics provides an alternate means to identify these genes. A form of haplotype association mapping (Pletcher et al, 2004) has recently been used to identify genes responsible for variation in complex biologies such as drug metabolism (Guo et al, 2006), tumor susceptibility (Liu et al, 2006), and liver fibrosis (Hillebrandt et al, 2005). The strain-dependent differences in baseline TST immobility and the behavioral response to antidepressants suggest that, provided a larger strain set, these traits will also be amenable to dissection by haplotype mapping.…”

Section: Discussionmentioning

confidence: 99%

Genetic Regulation of Behavioral and Neuronal Responses to Fluoxetine

Miller

Schultz

Gulati

et al. 2007

Neuropsychopharmacol

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Despite widespread use of antidepressants, the factors underlying the behavioral response to antidepressants are unknown. It has been shown that antidepressant treatment promotes the proliferation and survival of neurons in the adult hippocampus via enhanced serotonergic signaling, but it is unclear whether hippocampal neurogenesis is responsible for the behavioral response to antidepressants. Furthermore, a large subpopulation of patients fails to respond to antidepressant treatment due to presumed underlying genetic factors. In the present study, we have used the phenotypic and genotypic variability of inbred mouse strains to show that there is a genetic component to both the behavioral and neuronal effects of chronic fluoxetine treatment, and that this antidepressant induces an increase in hippocampal cell proliferation only in the strains that also show a positive behavioral response to treatment. Furthermore, the behavioral and neuronal responses are associated with an upregulation of genes known to promote neuronal proliferation and survival. These results suggest that inherent genetic predisposition to increased serotonin-induced neurogenesis may be a determinant of antidepressant efficacy.

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Section: Discussionmentioning

confidence: 99%

Genetic Regulation of Behavioral and Neuronal Responses to Fluoxetine

Miller

Schultz

Gulati

et al. 2007

Neuropsychopharmacol

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“…4‐hydroxyproline content was determined spectrophotometrically in liver hydrolysates as previously described in Hillebrandt et al. 50. For both assays 16 mice of each intervention group were included in the analysis.…”

Section: Methodsmentioning

confidence: 99%

Intermittent calorie restriction largely counteracts the adverse health effects of a moderate‐fat diet in aging C57BL/6J mice

Lute

Boekschoten

Dijk

et al. 2017

Molecular Nutrition Food Res

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ScopeCalorie restriction (CR) has been shown to extend life‐ and health‐span in model species. For most humans, a life‐long CR diet is too arduous to adhere to. The aim of this study was to explore whether weekly intermittent CR can (1) provide long‐term beneficial effects and (2) counteract diet‐induced obesity in male aging mice.Methods and resultsIn this study, we have exposed C57Bl/6J mice for 24 months to an intermittent (INT) diet, alternating weekly between CR of a control diet and ad libitum moderate‐fat (MF) feeding. This weekly intermittent CR significantly counteracted the adverse effects of the MF diet on mortality, body weight, and liver health markers in 24‐month‐old male mice. Hepatic gene expression profiles of INT‐exposed animals appeared much more comparable to CR‐ than to MF‐exposed mice. At 12 months of age, a subgroup of MF‐exposed mice was transferred to the INT diet. Gene expression profiles in the liver of the 24‐month‐old diet switch mice were highly similar to the INT‐exposed mice. However, a small subset of genes was consistently changed by the MF diet during the first phase of life.ConclusionWeekly intermittent CR largely, but not completely, reversed adverse effects caused by a MF diet.

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“…37,38 Deposits of C3 and IgM can be found at the dermal-epidermal junction in skin biopsies of patients with GVHD. 39 Although tissue deposition of complement would be expected to lead to lower levels of circulating complement, the inflammatory disease state of GVHD may theoretically result in a net increase in the synthesis of complement in response to cytokines such as IL-6. 40 Complement has been shown to stimulate other fibrotic processes, such as cirrhosis, by the expression of complement receptors on myofibroblasts in the liver.…”

Section: Org Frommentioning

confidence: 99%

Sclerotic-type chronic GVHD of the skin: clinical risk factors, laboratory markers, and burden of disease

Martires¹,

Baird

Steinberg

et al. 2011

Blood

103

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Chronic GVHD is one of the most severe complications of allogeneic HSCT. The sclerotic skin manifestations of cGVHD (ScGVHD) result from inflammation and fibrosis of the dermis, subcutaneous tissue, or fascia, leading to significant functional disability. Risk factors and clinical markers associated with ScGVHD remain largely unexamined. By using a singlevisit, cross-sectional design, we evaluated 206 patients with cGVHD at the National Institutes of Health. Most patients manifested severe (ie, 63% National Institutes of Health score "severe"), refractory disease (median treatments ‫؍‬ 4). ScGVHD was detected in 109 (52.9%) patients. ScGVHD was associated with greater platelet count (P < .001) and C3 (P < .001), and decreased forced vital capacity (P ‫؍‬ .013). Total body irradiation (TBI) was associated with development of ScGVHD (P ‫؍‬ .002). TBI administered in reduced-intensity conditioning was most strongly associated with ScGVHD (14/15 patients, P < .0001). Patients with ScGVHD had significant impairments of joint range of motion and grip strength (P < .001). Greater body surface area involvement was associated with poorer survival (P ‫؍‬ .015). We conclude that TBI, particularly in reduced-intensity regimens, may be an important risk factor for ScGVHD.

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Complement factor 5 is a quantitative trait gene that modifies liver fibrogenesis in mice and humans

Cited by 241 publications

References 47 publications

Genetic Regulation of Behavioral and Neuronal Responses to Fluoxetine

Genetic Regulation of Behavioral and Neuronal Responses to Fluoxetine

Intermittent calorie restriction largely counteracts the adverse health effects of a moderate‐fat diet in aging C57BL/6J mice

Sclerotic-type chronic GVHD of the skin: clinical risk factors, laboratory markers, and burden of disease

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