Differential effects on kidney and liver growth of a non-viral hGH-expression vector in hypophysectomized mice

Khamaisi, Mogher; Søndergaard, Morten; Segev, Yael; Dagnæs‐Hansen, Frederik; Jensen, Thomas G.; Landau, Danny; Flyvbjerg, Allan

doi:10.1016/j.ghir.2007.01.018

Cited by 10 publications

(8 citation statements)

References 24 publications

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“…While GH caused normalization of spleen mass in both virus doses, liver-albeit heavier than in Plac animals, did not fully normalize, suggesting that the growth of the liver requires higher GH levels than the spleen. The observation that liver growth requires GH fits nicely with our previous work in which GHD mice were treated with daily injections of recombinant mouse GH (Alba et al, 2005), as well as with work of others (Khamaisi et al, 2007). …”

Section: Discussionsupporting

confidence: 86%

Partial Rescue of Growth Failure in Growth Hormone (GH)-Deficient Mice by a Single Injection of a Double-Stranded Adeno-Associated Viral Vector Expressing the GH Gene Driven by a Muscle-Specific Regulatory Cassette

et al. 2009

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Growth hormone (GH) deficiency (GHD) causes somatic growth impairment. GH has a very short half-life and therefore it has to be administered by daily subcutaneous injections. Adeno-associated viral (AAV) vectors have been used to deliver genes to animals, and recently developed double stranded (ds)–AAV vectors provide widespread and stable transgene expression. In the present study we tested whether an intramuscular injection of ds-AAV vector expressing GH under the control of an M-creatine kinase regulatory cassette would assure sufficient systemic GH delivery in conjunction with muscle-specific expression. Virus-injected GHD mice showed a significant (p<0.05) increase in body length and body weight, without reaching full normalization, and significant (p<0.05) reduction in absolute and relative visceral fat. Quantitative RT-PCR showed preferential GH expression in skeletal muscles that was confirmed by qualitative fluorescence analysis in mice injected with a similar virus expressing GFP. The present study shows that systemic GH delivery to GHD animals is possible via a single intramuscular injection of dsAAV carrying a muscle-specific GH-expressing regulatory cassette.

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Section: Discussionsupporting

confidence: 86%

Partial Rescue of Growth Failure in Growth Hormone (GH)-Deficient Mice by a Single Injection of a Double-Stranded Adeno-Associated Viral Vector Expressing the GH Gene Driven by a Muscle-Specific Regulatory Cassette

et al. 2009

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“…Body weight at the end of the experiment was normalized to tibia length, because of the important body weight differences between HFD rats and controls. Tibia length is used to compare parameters in animals where the main variable in the model is body weight (Khamaisi et al, 2007;de las Heras et al, 2009;Xu et al, 2009).…”

Section: Methodsmentioning

confidence: 99%

Rosuvastatin restored adrenergic and nitrergic function in mesenteric arteries from obese rats

Blanco-Rivero

Heras

Martín-Fernández

et al. 2010

British J Pharmacology

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BACKGROUND AND PURPOSEWe investigated whether high-fat diet (HFD)-induced obesity was associated with changed function of components of the mesenteric innervation (adrenergic, sensory and nitrergic), the mechanisms involved and the possible effects of rosuvastatin on these changes. EXPERIMENTAL APPROACHMale Wistar rats were divided into three groups. (i) rats fed a standard diet (control group); (ii) rats fed a HFD (33.5% fat) for 7 weeks; and (iii) rats fed a HFD and treated with rosuvastatin (15 mg·kg) for 7 weeks. Segments of isolated mesenteric arteries were exposed to electric field stimulation (EFS) with or without tetrodotoxin, phentolamine, 7-nitroindazole (7NI) or N w nitro-L-arginine methyl ester (L-NAME). Noradrenaline, ATP and NO release, and nNOS expression were also measured. KEY RESULTSEFS induced a greater frequency-dependent contraction in obese than in control rats. In HFD rats, phentolamine reduced contractions elicited by EFS, but noradrenaline release was greater and ATP release decreased. L-NAME and 7NI increased contractions to EFS in segments from control rats, but not in those from HFD rats. NO release and nNOS expression were lower in arterial segments from HFD rats than in control rats. All these changes in HFD rats were reversed by treatment with rosuvastatin. CONCLUSIONS AND IMPLICATIONSNeural control of mesenteric vasomotor tone was altered in HFD rats. Enhanced adrenergic and diminished nitrergic components both contributed to increased vasoconstrictor responses to EFS. All these changes were reversed by rosuvastatin, indicating novel mechanisms of statins in neural regulation of vascular tone.

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“…3 The efficacy and safety of recombinant human growth hormone (rhGH) treatment has been proven in short children with chronic kidney disease who are on conservative treatment or undergone dialysis treatment. 4 Although there are some experimental studies 5,6 investigated the role of GH deficiency, rhGH, and IGF-1 on renal growth in animals, no clinical data has been reported up to date about the renal growth in rhGH received children. Therefore, in this study, we aimed to investigate the role of rhGH on kidney growth in children who receiving rhGH supplementation for at least 4 years period.…”

Section: Introductionmentioning

confidence: 99%

Kidney growth and renal functions under the growth hormone replacement therapy in children

et al. 2014

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Objective: The aim of this study was to investigate the kidney growth and renal functions in children receiving recombinant human growth hormone (rhGH) treatment. Materials and methods: A total of 37 children who received rhGH for 1.5 years before the study was started and 48 healthy controls were included at first evaluation. Hormone levels were determined and kidney sizes were measured by ultrasound. Kidney functions were assessed by serum creatinine and estimated glomerular filtration rate (eGFR). After 3 years of first evaluation, 23 patients were re-assessed. Results: Kidney sizes were found to be lower in rhGH received children compared with controls at first evaluation (p50.05). Significant positive correlations were found between anthropometric measurements and kidney length and kidney volume (p50.05). Height was the most significant predictor of kidney volume in rhGH received children (p50.001). After 3-years of follow-up significantly increases were found in kidney length and volume compared with the first measurements (p50.05). Increase percentage of body height was similar to increasing percent of kidney length and liver long axis (14.2%, 11.7.1% and 7.7%, respectively, p40.05). Although no abnormal renal function test results were found at first and second evaluations; rhGH received children had significantly lower eGFR, at first evaluation, compared with controls; however, renal functions significantly increased after 3 years of followup (p50.05). Conclusions: In conclusion, effect rhGH treatment on kidney growth is parallel to growth in body height and other visceral organs. A 3-years rhGH treatment resulted in significant increases in renal functions.

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Differential effects on kidney and liver growth of a non-viral hGH-expression vector in hypophysectomized mice

Cited by 10 publications

References 24 publications

Partial Rescue of Growth Failure in Growth Hormone (GH)-Deficient Mice by a Single Injection of a Double-Stranded Adeno-Associated Viral Vector Expressing the GH Gene Driven by a Muscle-Specific Regulatory Cassette

Partial Rescue of Growth Failure in Growth Hormone (GH)-Deficient Mice by a Single Injection of a Double-Stranded Adeno-Associated Viral Vector Expressing the GH Gene Driven by a Muscle-Specific Regulatory Cassette

Rosuvastatin restored adrenergic and nitrergic function in mesenteric arteries from obese rats

Kidney growth and renal functions under the growth hormone replacement therapy in children

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