Fibroblast growth factor-23-mediated inhibition of renal phosphate transport in mice requires sodium-hydrogen exchanger regulatory factor-1 (NHERF-1) and synergizes with parathyroid hormone

10.1074/jbc.M111.288357Journal of Biological Chemistry2864337216-37221JBCH

NHERF1 over-expression modulates CFTR expression and activity in human airway 16HBE14o- cells and rescues ∆F508 CFTR functional expression in cystic fibrosis cells

There is evidence that cystic fibrosis transmembrane conductance regulator (CFTR) interacting proteins play critical roles in the proper expression and function of CFTR. The Na(+)/H(+) exchanger regulatory factor isoform 1 (NHERF1) was the first identified CFTR-binding protein. Here we further clarify the role of NHERF1 in the regulation of CFTR activity in two human bronchial epithelial cell lines: the normal, 16HBE14o-, and the homozygous DeltaF508 CFTR, CFBE41o-. Confocal analysis in polarized cell monolayers demonstrated that NHERF1 distribution was associated with the apical membrane in 16HBE14o- cells while being primarily cytoplasmic in CFBE41o- cells. Transfection of 16HBE14o- monolayers with vectors encoding for wild-type (wt) NHERF1 increased both apical CFTR expression and apical protein kinase A (PKA)-dependent CFTR-mediated chloride efflux, whereas transfection with NHERF1 mutated in the binding groove of the PDZ domains or truncated for the ERM domain inhibited both the apical CFTR expression and the CFTR-dependent chloride efflux. These data led us to hypothesize an important role for NHERF1 in regulating CFTR localization and stability on the apical membrane of 16HBE14o- cell monolayers. Importantly, wt NHERF1 overexpression in confluent DeltaF508 CFBE41o- and DeltaF508 CFT1-C2 cell monolayers induced both a significant redistribution of CFTR from the cytoplasm to the apical membrane and a PKA-dependent activation of CFTR-dependent chloride secretion

Urine electrolyte, mineral, and protein excretion in NHERF-2 and NHERF-1 null mice.

Contains fulltext : 69456.pdf (publisher's version ) (Closed access)The adaptor proteins sodium/hydrogen exchanger regulatory factor (NHERF)-1 and NHERF-2 have overlapping tissue distribution in renal cells and overlapping specificity in their binding to renal transporters and other proteins. To compare the kidney-specific differences in the function of these adaptor proteins, NHERF-1 and NHERF-2 null mice were compared with wild-type control mice. In NHERF-2 null mice, the renal proximal tubule abundance and distribution of NHERF-1 and NHERF-3 were not different from those in wild-type animals. The glomerular expression of podocalyxin and ZO-1 also did not differ. NHERF-1 null mice had increased urinary excretion of phosphate, calcium, and uric acid compared with wild-type control and NHERF-2 null mice. Because of the association between NHERF-2 and podocalyxin in glomeruli and ClC-5 in the renal proximal tubule, the urinary excretion of protein was determined. There were no differences in the urinary excretion of protein or low-molecular-weight proteins between wild-type control, NHERF-1(-/-), and NHERF-2(-/-) mice. These studies indicate that the increased urinary excretion of phosphate and uric acid are specific to NHERF-1 null mice and highlight the fact that predictions about the role of adaptor proteins such as the NHERF proteins obtained from studies of model cell systems must be confirmed in whole animals

Beliefs of Health Care Providers, Lay Health Care Providers and Lay Persons in Nigeria Regarding Hypertension. A Systematic Mixed Studies Review

<div><p>Background</p><p>Hypertension is a major health risk factor for mortality globally, resulting in about 13% of deaths worldwide. In Nigeria, the high burden of hypertension remains an issue for urgent attention. The control of hypertension, among other factors, is strongly determined by personal beliefs about the illness and recommended treatment.</p><p>Objective</p><p>The aim of this review is to systematically synthesize available data from all types of studies on beliefs of the Nigerian populace about hypertension</p><p>Methods</p><p>We searched the following electronic databases; Medline, EMBase, PsycInfo, AMED from their inception till date for all relevant articles. A modified Kleinman’s explanatory model for hypertension was used as a framework for extraction of data on beliefs about hypertension.</p><p>Results</p><p>The search yielded a total of 3,794 hits from which 16 relevant studies (2 qualitative, 11 quantitative and 3 mixed methods studies) met the inclusion criteria for the review. Overall, most health care providers (HCPs) believe that stress is a major cause of hypertension. Furthermore, reported cut-off point for uncomplicated hypertension differed widely among HCPs. Lay Health Care Providers such as Patent Medicine Vendors’ beliefs about hypertension seem to be relatively similar to health care professionals in areas of risk factors for hypertension, course of hypertension and methods of treatment. Among Lay persons, misconception about hypertension was quite high. Although some Nigerians believed that life style habits such as alcohol intake, exercise levels, cigarette smoking were risk factors for developing hypertension, there was discordance between belief and practice of control of risk factors. However, beliefs across numerous ethnic groups and settings (urban/rural) in Nigeria have not been explored.</p><p>Conclusion</p><p>In order to achieve control of hypertension in Nigeria, interventions should be informed, among other factors, by adequate knowledge of beliefs regarding hypertension across the numerous ethnic groups in Nigeria, settings (rural/urban), age and sex.</p></div