Ghrelin suppresses migration of macrophages via inhibition of ROCK2 under chronic intermittent hypoxia

Chen, Hong; Du, Ji-Zeng; Zhang, Siying; Tu, Hao; Zhang, Man

doi:10.1177/0300060520926065

Cited by 3 publications

(1 citation statement)

References 34 publications

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“…25 For example, by inhibiting myosin phosphatase, Rho-kinase increases phosphorylation of the myosin light chain, resulting in smooth muscle cell contraction and vasospasm. 26,27 Its activity is found to be involved in macrophage and neutrophil migration, 28,29 possibly through cytoskeletal rearrangement and adhesion molecule expression. Moreover, Rho-kinase inhibition can increase anti-inflammatory cytokine production and phagocytosis activities of macrophages., 30,31 indicating its role in M2-type differentiation.…”

Section: Introductionmentioning

confidence: 99%

Rho-Kinase inhibition decreases focal cerebral ischemia-induced glial activation in rats

Sheikh

Yano

Mitaki

et al. 2022

J Cent Nerv Syst Dis

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Background Rho-kinase inhibition in a rat middle cerebral artery occlusion (MCAO) model is reported to improve neurological functions and decrease infarction size. Objective The objective of this study is to investigate the underlying mechanisms of such improvement by evaluating the effects of Rho-kinase inhibition on astrocytes and microglial accumulation and activation in this condition. Methods Adult male Sprague-Dawley (SD) rats were used to generate the MCAO model, which received an I.P injection of a chemical Rho-kinase inhibitor (Fasudil- 5 mg/kg/day) or vehicle (PBS) for 2 and 4 days. Results Fasudil treatment significantly decreased the stroke volumes and water content in the lesion areas, as revealed by MRI. Immunostaining and Western blotting results demonstrated that Fasudil significantly decreased the levels of Aquaporin-4, a water channel protein. The number of GFAP+ astrocytes and Iba-1+ macrophage/microglia was decreased in the lesion areas. Proinflammatory transcription factor NF-κB protein levels were decreased in the Fasudil group 2 days after MCAO. Also, proinflammatory mediators including TNF-α, IL-1β, and iNOS levels were decreased. In vitro migration study using a human microglial cell line (HMO6) confirmed the inhibitory effects of Fasudil on the process. Fasudil also decreased combined IL-1β and IFNγ-induced NF-κB nuclear translocation in HMO6. Moreover, Fasudil transiently decreased combined IL-1β and IFNγ-induced iNOS, TNFα, and IL-1β mRNA levels in HMO6. Conclusion Our study demonstrates the inhibitory effects of Rho-kinase on NF-κB-mediated glial activation and cerebral edema, which might be a promising therapeutic target in acute cerebral ischemia conditions.

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Section: Introductionmentioning

confidence: 99%

Rho-Kinase inhibition decreases focal cerebral ischemia-induced glial activation in rats

Sheikh

Yano

Mitaki

et al. 2022

J Cent Nerv Syst Dis

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Research Progress of Obstructive Sleep Apnea Syndrome and Atherosclerosis

游¹

2022

ACM

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Alternative splicing signature of alveolar type II epithelial cells of Tibetan pigs under hypoxia-induced

et al. 2022

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Alternative splicing (AS) allows the generation of multiple transcript variants from a single gene and a ects biological processes by generating protein diversity in organisms. In total, , AS events corresponding to , genes were identified, and SE is the most abundant alternatively spliced type. The analysis of functional categories demonstrates that alternatively spliced di erentially expressed genes (DEGs) were enriched in the MAPK signaling pathway and hypoxia-inducible factor (HIF-) signaling pathway. Proteoglycans in cancer between the normoxic ( % O , TN and LN) and hypoxic ( % O , TL and LL) groups, such as SLC A , HK , HK , ENO , and PFKFB , have the potential to rapidly proliferate alveolar type II epithelial (ATII) cells by increasing the intracellular levels of glucose and quickly divert to anabolic pathways by glycolysis intermediates under hypoxia. ACADL, EHHADH, and CPT A undergo one or two AS types with di erent frequencies in ATII cells between TN and TL groups (excluding alternatively spliced DEGs shared between normoxic and hypoxic groups), and a constant supply of lipids might be obtained either from the circulation or de novo synthesis for better growth of ATII cells under hypoxia condition. MCM and MCM undergo di erent AS types between LN and LL groups (excluding alternatively spliced DEGs shared between normoxic and hypoxic groups), which may bind to the amino-terminal PER-SIM-ARNT domain and the carboxyl terminus of HIFα to maintain their stability. Overall, AS and expression levels of candidate mRNAs between Tibetan pigs and Landrace pigs revealed by RNA-seq suggest their potential involvement in the ATII cells grown under hypoxia conditions.

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Ghrelin suppresses migration of macrophages via inhibition of ROCK2 under chronic intermittent hypoxia

Cited by 3 publications

References 34 publications

Rho-Kinase inhibition decreases focal cerebral ischemia-induced glial activation in rats

Rho-Kinase inhibition decreases focal cerebral ischemia-induced glial activation in rats

Research Progress of Obstructive Sleep Apnea Syndrome and Atherosclerosis

Alternative splicing signature of alveolar type II epithelial cells of Tibetan pigs under hypoxia-induced

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