Adrenocorticotropic hormone ameliorates acute kidney injury by steroidogenic-dependent and -independent mechanisms

Jin, Si; Ge, Yan; Zhuang, Songlin; Wang, Li Juan; Chen, Shan; Gong, Rujun

doi:10.1038/ki.2012.447

Cited by 37 publications

(44 citation statements)

References 45 publications

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“…29,30,46 Finally, Acthar could prevent progression of proteinuria in the NZB/W F1 model via direct effects on podocytes, as prior evidence demonstrates MCR expression on podocytes, as well as protective effects of this drug on proteinuria in both animal and human nephrotic disease. 11,16,18 Of note, in these experiments, Acthar treatment was not associated with any identified adverse events. In contrast, prednisolone-treated NZB/W F1 mice failed to gain weight throughout the treatment period, and were more likely to require early termination from the study.…”

Section: Discussionmentioning

confidence: 86%

Immunomodulatory effects of H.P. Acthar Gel on B cell development in the NZB/W F1 mouse model of systemic lupus erythematosus

Da¹,

Grant

Oh³

et al. 2014

Lupus

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H.P. Acthar Gel® (Acthar) is a highly purified repository gel preparation of adrenocorticotropic hormone (ACTH1-39), a melanocortin peptide that can bind and activate specific receptors expressed on a range of systemic lupus erythematosus (SLE)-relevant target cells and tissues. This study was performed to evaluate the effects of Acthar in a mouse model of SLE, using an F1 hybrid of the New Zealand Black and New Zealand White strains (NZB/W F1). Twenty-eight week old NZB/W F1 mice with established autoimmune disease were treated with Acthar, Placebo Gel (Placebo), or prednisolone and monitored for 19 weeks. Outcomes assessed included disease severity (severe proteinuria, ≥ 20% body weight loss, or prostration), measurement of serial serum autoantibody titers, terminal spleen immunophenotyping, and evaluation of renal histopathology. Acthar treatment was linked with evidence of altered B cell differentiation and development, manifested by a significant reduction in splenic B cell follicular and germinal center cells, and decreased levels of circulating total and anti-double-stranded DNA (IgM, IgG, and IgG2a) autoantibodies as compared with Placebo. Additionally, Acthar treatment resulted in a significant decrease of proteinuria, reduced renal lymphocyte infiltration, and attenuation of glomerular immune complex deposition. These data suggest that Acthar diminished pathogenic autoimmune responses in the spleen, peripheral blood, and kidney of NZB/W F1 mice. This is the first preclinical evidence demonstrating Acthar's potential immunomodulatory activity and efficacy in a murine model of systemic lupus erythematosus.

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Section: Discussionmentioning

confidence: 86%

Immunomodulatory effects of H.P. Acthar Gel on B cell development in the NZB/W F1 mouse model of systemic lupus erythematosus

Da¹,

Grant

Oh³

et al. 2014

Lupus

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“…In a rat model of tumor necrosis factor (TNF)-induced acute kidney injury, Si et al (2013) found that ACTH gel prevented kidney injury, corrected acute renal dysfunction, and improved survival. Morphologically, ACTH gel ameliorated TNF-induced acute tubular necrosis, associated with a reduction in tubular apoptosis.…”

Section: Acth Also Has a Renoprotective Effect In Chronic Kidney Diseasementioning

confidence: 99%

60 YEARS OF POMC: Adrenal and extra-adrenal functions of ACTH

Gallo‐Payet

2016

Journal of Molecular Endocrinology

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The pituitary adrenocorticotropic hormone (ACTH) plays a pivotal role in homeostasis and stress response and is thus the major component of the hypothalamo–pituitary–adrenal axis. After a brief summary of ACTH production from proopiomelanocortin (POMC) and on ACTH receptor properties, the first part of the review covers the role of ACTH in steroidogenesis and steroid secretion. We highlight the mechanisms explaining the differential acute vs chronic effects of ACTH on aldosterone and glucocorticoid secretion. The second part summarizes the effects of ACTH on adrenal growth, addressing its role as either a mitogenic or a differentiating factor. We then review the mechanisms involved in steroid secretion, from the classical Cyclic adenosine monophosphate second messenger system to various signaling cascades. We also consider how the interaction between the extracellular matrix and the cytoskeleton may trigger activation of signaling platforms potentially stimulating or repressing the steroidogenic potency of ACTH. Finally, we consider the extra-adrenal actions of ACTH, in particular its role in differentiation in a variety of cell types, in addition to its known lipolytic effects on adipocytes. In each section, we endeavor to correlate basic mechanisms of ACTH function with the pathological consequences of ACTH signaling deficiency and of overproduction of ACTH.

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“…Urine creatinine was measured by a creatinine assay kit (BioAssay Systems, Hayward, CA). Blood pressure was measured using the tail cuff method as described previously (41). Mice were sacrificed on day 3, 7, 14, or 28.…”

Section: Animal Experimental Designmentioning

confidence: 99%

“…Tetrazolium was released by dimethyl sulfoxide, and the optical density was determined with a spectrophotometer at 570 nm reader as before (41).…”

Section: Tetrazolium Assay For Cellular Viabilitymentioning

confidence: 99%

Glycogen Synthase Kinase 3β Orchestrates Microtubule Remodeling in Compensatory Glomerular Adaptation to Podocyte Depletion

Liu

et al. 2015

Journal of Biological Chemistry

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Background: Microtubule dynamics is involved in podocyte morphogenesis. Results: The microtubule-associated proteins Tau and CRMP2 are regulated by GSK3␤ in podocytes. Blockade of GSK3␤ ameliorates podocyte injury and proteinuria. Conclusion: The GSK3␤-dictated microtubule remodeling is crucial for the compensatory glomerular adaptation to podocyte loss. Significance: Inhibition of GSK3␤ might represent a novel therapeutic strategy to treat podocytopathy.

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Adrenocorticotropic hormone ameliorates acute kidney injury by steroidogenic-dependent and -independent mechanisms

Cited by 37 publications

References 45 publications

Immunomodulatory effects of H.P. Acthar Gel on B cell development in the NZB/W F1 mouse model of systemic lupus erythematosus

Immunomodulatory effects of H.P. Acthar Gel on B cell development in the NZB/W F1 mouse model of systemic lupus erythematosus

60 YEARS OF POMC: Adrenal and extra-adrenal functions of ACTH

Glycogen Synthase Kinase 3β Orchestrates Microtubule Remodeling in Compensatory Glomerular Adaptation to Podocyte Depletion

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