scholarly journals ROCK Inhibition – A New Therapeutic Avenue in Kidney Protection

10.5772/19200 ◽  
2011 ◽  
Author(s):  
Stefan Reuter ◽  
Dominik Kentrup ◽  
Eckhart Bussemaker
Keyword(s):  
Kidney Protection ◽  
Rock Inhibition ◽  
Therapeutic Avenue

scholarly journals Nicotinamide promotes pancreatic differentiation through the dual inhibition of CK1 and ROCK kinases in human embryonic stem cells

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yumeng Zhang ◽  
Jiaqi Xu ◽  
Zhili Ren ◽  
Ya Meng ◽  
Weiwei Liu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Fate ◽  
Human Embryonic Stem Cells ◽  
Embryonic Stem ◽  
Cell Fate Determination ◽  
Rna Seq ◽  
Pancreatic Cell ◽  
Pancreatic Progenitor ◽  
Pancreatic Progenitors ◽  
Rock Inhibition

Abstract Background Vitamin B3 (nicotinamide) plays important roles in metabolism as well as in SIRT and PARP pathways. It is also recently reported as a novel kinase inhibitor with multiple targets. Nicotinamide promotes pancreatic cell differentiation from human embryonic stem cells (hESCs). However, its molecular mechanism is still unclear. In order to understand the molecular mechanism involved in pancreatic cell fate determination, we analyzed the downstream pathways of nicotinamide in the derivation of NKX6.1+ pancreatic progenitors from hESCs. Methods We applied downstream modulators of nicotinamide during the induction from posterior foregut to pancreatic progenitors, including niacin, PARP inhibitor, SIRT inhibitor, CK1 inhibitor and ROCK inhibitor. The impact of those treatments was evaluated by quantitative real-time PCR, flow cytometry and immunostaining of pancreatic markers. Furthermore, CK1 isoforms were knocked down to validate CK1 function in the induction of pancreatic progenitors. Finally, RNA-seq was used to demonstrate pancreatic induction on the transcriptomic level. Results First, we demonstrated that nicotinamide promoted pancreatic progenitor differentiation in chemically defined conditions, but it did not act through either niacin-associated metabolism or the inhibition of PARP and SIRT pathways. In contrast, nicotinamide modulated differentiation through CK1 and ROCK inhibition. We demonstrated that CK1 inhibitors promoted the generation of PDX1/NKX6.1 double-positive pancreatic progenitor cells. shRNA knockdown revealed that the inhibition of CK1α and CK1ε promoted pancreatic progenitor differentiation. We then showed that nicotinamide also improved pancreatic progenitor differentiation through ROCK inhibition. Finally, RNA-seq data showed that CK1 and ROCK inhibition led to pancreatic gene expression, similar to nicotinamide treatment. Conclusions In this report, we revealed that nicotinamide promotes generation of pancreatic progenitors from hESCs through CK1 and ROCK inhibition. Furthermore, we discovered the novel role of CK1 in pancreatic cell fate determination.

scholarly journals Potential kidney protection with liraglutide and semaglutide – exploratory mediation analysis

2021 ◽  
Author(s):  
Johannes F. E. Mann ◽  
John B. Buse ◽  
Thomas Idorn ◽  
Lawrence A. Leiter ◽  
Richard E. Pratley ◽  
...  
Keyword(s):  
Mediation Analysis ◽  
Kidney Protection

scholarly journals ROCK inhibition with Fasudil induces beta-catenin nuclear translocation and inhibits cell migration of MDA-MB 231 human breast cancer cells

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Fabiana Sélos Guerra ◽  
Ramon Guerra de Oliveira ◽  
Carlos Alberto Manssour Fraga ◽  
Claudia dos Santos Mermelstein ◽  
Patricia Dias Fernandes
Keyword(s):  
Breast Cancer ◽  
Cell Migration ◽  
Cancer Cells ◽  
Human Breast Cancer ◽  
Breast Cancer Cells ◽  
Nuclear Translocation ◽  
Beta Catenin ◽  
Human Breast Cancer Cells ◽  
Human Breast ◽  
Rock Inhibition

scholarly journals ROCK inhibition enhances microRNA function by promoting deadenylation of targeted mRNAs via increasing PAIP2 expression

2015 ◽  
Vol 43 (15) ◽  
pp. 7577-7589 ◽  
Author(s):  
Takeshi Yoshikawa ◽  
Jianfeng Wu ◽  
Motoyuki Otsuka ◽  
Takahiro Kishikawa ◽  
Motoko Ohno ◽  
...  
Keyword(s):  
Rock Inhibition ◽  
Microrna Function

scholarly journals ROCK inhibition stimulates SOX9/Smad3-dependent COL2A1 expression in inner meniscus cells

2016 ◽  
Vol 21 (4) ◽  
pp. 524-529 ◽  
Author(s):  
Takayuki Furumatsu ◽  
Ami Maehara ◽  
Toshifumi Ozaki
Keyword(s):  
Col2a1 Expression ◽  
Meniscus Cells ◽  
Rock Inhibition

Cardiometabolic and Kidney Protection in Kidney Transplant Recipients with Diabetes

2021 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Vikas S. Sridhar ◽  
Jaya Prakash N. Ambinathan ◽  
Pieter Gillard ◽  
Chantal Mathieu ◽  
David Z.I. Cherney ◽  
...  
Keyword(s):  
Kidney Transplant ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Kidney Protection
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