Cyclic Nucleotide Signalling in Kidney Fibrosis

Schinner, Elisabeth; Wetzl, Veronika; Schlossmann, Jens

doi:10.3390/ijms16022320

Cited by 46 publications

(49 citation statements)

References 185 publications

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“…3D, E). Regarding the mechanism of antifibrotic effect of PDE4 inhibitor, Elisabeth Schinner et al (35) reviewed effects and mechanisms of cAMP on renal fibrosis. An increase in cAMP levels exerts antifibrotic effects in fibrosis that are mediated by stimulation of PKA and activated cAMP response element binding protein, which blocks TGF-b-mediated profibrotic gene transcription.…”

Section: Discussionmentioning

confidence: 99%

Phosphodiesterase 4 inhibitor and phosphodiesterase 5 inhibitor combination therapy has antifibrotic and anti‐inflammatory effects in mdx mice with Duchenne muscular dystrophy

et al. 2017

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Duchenne muscular dystrophy (DMD) is the most common inherited muscular dystrophy. Patients experience DMD in their 20s from cardiac or respiratory failure related to progressive muscle wasting. Currently, the only treatments for the symptoms of DMD are available. Muscle fibrosis, a DMD feature, leads to reduced muscle function and muscle mass, and hampers pharmaceutical therapeutic efficacy. Although antifibrotic agents may be useful, none is currently approved. Phosphodiesterase 4 (PDE4) inhibitors have exhibited antifibrotic effects in human and animal models. In this study, we showed beneficial effects of the PDE4 inhibitor piclamilast in the DMD mdx mouse. Piclamilast reduced the mRNA level of profibrotic genes, including collagen 1A1, in the gastrocnemius and diaphragm, in the mdx mouse, and significantly reduced the Sirius red staining area. The PDE5 inhibitors sildenafil and tadalafil ameliorated functional muscle ischemia in boys with DMD, and sildenafil reversed cardiac dysfunction in the mdx mouse. Single-treatment piclamilast or sildenafil showed similar antifibrotic effects on the gastrocnemius; combination therapy showed a potent antifibrotic effect, and piclamilast and combination therapy increased peroxisome proliferator-activated receptor γ coactivator-1α mRNA in mouse gastrocnemius. In summary, we confirmed that piclamilast has significant antifibrotic effects in mdx mouse muscle and is a potential treatment for muscle fibrosis in DMD.-Nio, Y., Tanaka, M., Hirozane, Y., Muraki, Y., Okawara, M., Hazama, M., Matsuo, T. Phosphodiesterase 4 inhibitor and phosphodiesterase 5 inhibitor combination therapy has antifibrotic and anti-inflammatory effects in mdx mice with Duchenne muscular dystrophy.

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Section: Discussionmentioning

confidence: 99%

Phosphodiesterase 4 inhibitor and phosphodiesterase 5 inhibitor combination therapy has antifibrotic and anti‐inflammatory effects in mdx mice with Duchenne muscular dystrophy

et al. 2017

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“…cAMP is involved in all aspect of renal physiology, and abnormal cAMP signaling has been linked to various kidney disorders including polycystic kidney diseases (PKDs), chronic kidney fibrosis, and renal failure (914,1036). PKDs are a family of genetic disorders involving the formation of noncancerous cyst clusters within a patient's kidney.…”

Section: F Epac and Kidney Diseasesmentioning

confidence: 99%

Intracellular cAMP Sensor EPAC: Physiology, Pathophysiology, and Therapeutics Development

Robichaux

Cheng

2018

Physiological Reviews

153

226

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This review focuses on one family of the known cAMP receptors, the exchange proteins directly activated by cAMP (EPACs), also known as the cAMP-regulated guanine nucleotide exchange factors (cAMP-GEFs). Although EPAC proteins are fairly new additions to the growing list of cAMP effectors, and relatively "young" in the cAMP discovery timeline, the significance of an EPAC presence in different cell systems is extraordinary. The study of EPACs has considerably expanded the diversity and adaptive nature of cAMP signaling associated with numerous physiological and pathophysiological responses. This review comprehensively covers EPAC protein functions at the molecular, cellular, physiological, and pathophysiological levels; and in turn, the applications of employing EPAC-based biosensors as detection tools for dissecting cAMP signaling and the implications for targeting EPAC proteins for therapeutic development are also discussed.

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“…In contrast, NO and its metabolites (e.g., peroxynitrate) cause oxidative stress and DNA damage, and they convert fibroblasts to a myofibroblast-like phenotype with fibrotic activity [42,43]. Second, cGMP is also produced by the natriuretic peptide (NP)/ particulate guanylyl cyclase (pGC) pathway, but sGC stimulators do not activate that pathway [44]. However, the contribution of the NP/pGC pathway to cGMP production is unknown, given that the levels of serum natriuretic peptides such as BNP in SSc patients tend to be higher than those in healthy individuals, and PDE5 inhibitors might be more potent cGMP-induction agents than sGC stimulators [45].…”

Section: Accepted Manuscriptmentioning

confidence: 99%

Sildenafil attenuates the fibrotic phenotype of skin fibroblasts in patients with systemic sclerosis

Higuchi

Kawaguchi

Takagi

et al. 2015

Clinical Immunology

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Cyclic Nucleotide Signalling in Kidney Fibrosis

Cited by 46 publications

References 185 publications

Phosphodiesterase 4 inhibitor and phosphodiesterase 5 inhibitor combination therapy has antifibrotic and anti‐inflammatory effects in mdx mice with Duchenne muscular dystrophy

Phosphodiesterase 4 inhibitor and phosphodiesterase 5 inhibitor combination therapy has antifibrotic and anti‐inflammatory effects in mdx mice with Duchenne muscular dystrophy

Intracellular cAMP Sensor EPAC: Physiology, Pathophysiology, and Therapeutics Development

Sildenafil attenuates the fibrotic phenotype of skin fibroblasts in patients with systemic sclerosis

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