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Anatomy and Embryology of the Mouth and Dentition
Published in John C Watkinson, Raymond W Clarke, Terry M Jones, Vinidh Paleri, Nicholas White, Tim Woolford, Head & Neck Surgery Plastic Surgery, 2018
With growth of the palatal shelves, there is considerable heterogeneity along the anteroposterior and mediolateral axes of molecules such as Shh, Bmp4, Msx1, Osr1, Barx1. However, the biochemical changes produced by the particular genes, growth factors and signalling molecules are poorly understood.
Genetic Basis of Blood Pressure and Hypertension
Published in Giuseppe Mancia, Guido Grassi, Konstantinos P. Tsioufis, Anna F. Dominiczak, Enrico Agabiti Rosei, Manual of Hypertension of the European Society of Hypertension, 2019
Sandosh Padmanabhan, Alisha Aman, Anna F. Dominiczak
Na+ reabsorption is controlled by mineralocorticoid active steroid hormones in both the distal convoluted tubule and the collecting duct (Figure 7.1). The amiloride-sensitive epithelial Na+ channel (ENaC; SCNN1A, SCNN1B, SCNN1G, SCNN1D) is found predominantly in principal cells of the collecting duct and the thiazide-sensitive sodium chloride cotransporter (NCC; SLC12A3) in the distal convoluted tubule. In addition, basolateral sodium-potassium adenosine triphosphate (ATP1A1-3, ATP1B1-4) and the luminal renal outer medulla K+ channel (ROMK; KCNJ1) are responsible for Na+ and K+ homeostasis. Aldosterone binds to the cytosolic mineralocorticoid receptor (MR; NR3C2) and leads to increased activity of the apical Na+ transporter, ENaC. Deoxycorticosterone and deoxycortisol and their metabolites are alternative agonists of the MR, with cortisol being the most important one. The 11β-hydroxysteroid dehydrogenase type 2 enzyme (HSD11B2), which converts active cortisol to the inactive cortisone, protects the MR from cortisol, an alternative agonist of the MR, thus establishing the aldosterone specificity of the MR. Additional regulatory elements that are involved include, but are not limited to, WNK (with no lysine) kinases – a family of large serine/threonine protein kinases (WNK1 and WNK4) (52). While WNK1 is widely expressed, WNK4 is expressed primarily in the kidney, localized to tight junctions. WNK4 is responsible for tonic inhibition of the thiazide-sensitive Na+ channel (SLC12A3), while WNK1 is a negative regulator of WNK4. WNK1 also activates NCC (SLC12A3), ENaC (SCNN1A, SCNN1B, SCNN1G, SCNN1D), and inhibits the renal K+ channel ROMK (KCNJ1) (52,53). Under hyperosmotic or hypotonic low-Cl− conditions, WNK isoforms are activated, and subsequently phosphorylate and activate the related protein kinases SPAK (STK39) and OSR1 (OXSR1) (54). SPAK and OSR1 phosphorylate and activate ion cotransporters that include NCC, NKCC1 (SLC12A2) and NKCC2 (SLC12A1), which are targets for the commonly thiazide-diuretic and loop-diuretic drugs, the former being an excellent antihypertensive drug (55).
OSR1 suppresses acute myeloid leukaemia cell proliferation by inhibiting LGR5-mediated JNK signalling
Published in Autoimmunity, 2021
OSR1 is a member of the zinc finger transcription factor family and functions as a transcriptional suppressor of oncogenic genes that are involved in the cell cycle and tumour growth [6]. OSR1 is generally considered as a tumour suppressor in gastric cancer due to the hypermethylation [13]. OSR1 promoted p53 transcription to increase p53 and p21, while decrease cyclin D1 and cyclin-dependent kinase 4, thus suppressing the cell cycle in gastric cancer [13]. Although the anti-cancer role of OSR1 has currently been investigated in diverse cancers, the regulatory role and mechanism in acute myeloid leukaemia are not completely understood.