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Human airway epithelial cell pH regulatory proteins in cystic fibrosis: Differential expression in nasal and bronchial airway cells
(2023-08-25) Davis, Michael D; Gaston, Benjamin; Smith, Laura; Rahman, Rania Abdul; Khalid, Faiza; Cotton, Calvin; Chmiel, James; Boyne, Katie; Ramsey, I Scott; Marozkina, Nadzeya
Background. Decreased apical bicarbonate transport into the airway surface liquid (ASL) has been associated with decreased ASL pH in some studies. Low ASL pH can have adverse respiratory effects. However, the human CF epithelium can also normalize ASL pH. We hypothesized that pH regulatory proteins other than the CF transmembrane regulator (CFTR) would be upregulated in the CF epithelium.
Methods. We grew primary human nasal and bronchial epithelial cells from healthy controls and CF subjects at air-liquid interface; each culture was grown until fully mature and ciliated (~ six weeks). We used immunoblotting to measure expression of proteins that can affect pH known in the airway, renal tubule and/or gut: carbonic anhydrases (CA) 1, 2 and 12; voltage-gated proton channel (Hv1); lactate dehydrogenases (LDH) A, B, and D; dual oxidases (DUOX) 1 and 2; Na+/H+ exchange regulatory factor; potassium-transporting ATPase alpha chain 2 (ATP12A), S-nitrosoglutathione reductase (GSNOR); glutaminase; and vacuolar-type ATPase (VTP-ase). Proteins that were differentially expressed were localized using cell fractionation and by immunofluorescence.
Results. There were no differences in expression of any of the proteins studied between healthy control and CF nasal epithelial cells. On the other hand, Hv1, CA1, CA2, CA12, LDHa, LDHd, ATP12a and GSNOR expression were each increased in the CF bronchial epithelium relative to the healthy control. Hv1 and CA2 were expressed in both cell membrane and cytoplasm, whereas CA1 and CA12 were cytoplasmic and nuclear. RNASeq data suggested that the differences in expression were post-transcriptional.
Conclusions. In the renal tubule and gut, mechanisms regulating luminal pH are well understood. In the airway, absence of CFTR can in some cases lead to ASL acidification; but other pH regulatory proteins are not well-studied. Here, we show increased expression of CA’s, LDH’s, ATP12a, GSNOR and Hv1 in bronchial epithelium from patients with CF. We speculate that these proteins could serve to normalize the CF epithelial pH. Nasal cells did not have these changes, arguing against the hypothesis that nasal epithelial gene expression results can uniformly be extrapolated to understand the biology of bronchial epithelium. These data also allow us to begin to create a map of pH regulatory systems in the human airway epithelium.
MYSTERY OF OUT OF HOSPITAL CARDIAC ARREST IN A PATIENT WITH INTERSTITIAL LUNG DISEASE
(Elsevier, 2020-10-01) Kyaw, Phyo; Massutti, Thomas; Abedrabo, Sabree; Sreedhar, Rajagopal; Foray, Nathalie
STRAIGHT TO THE LUNGS: UNUSUAL ETIOLOGY OF BILATERAL PULMONARY OPACITIES
(Elsevier, 2020-10-01) Massutti, Thomas; Kyaw, Phyo; White, Peter
2024 Indiana Pharmacist Workforce Data Report
(Indiana University School of Medicine, 2026-03-10) Dietz, Cleveland; Vaughn, Sierra; Daulton, Brittany
This report examines Indiana's pharmacist workforce based on 2024 license renewal data. Of 12,663 renewed licenses, 6,142 pharmacists actively practice in Indiana or provide telepharmacy services. The analysis covers demographics, education and training, employment characteristics, practice settings, populations served, services provided, and geographic distribution across Indiana's 92 counties. Key findings include workforce composition by age, gender, and race; qualifying education pathways; residency and fellowship completion rates; primary practice fields; and population-to-pharmacist ratios by county. The data reveal workforce patterns, service delivery methods, and geographic distribution disparities that inform understanding of pharmacy practice in Indiana.
Pioneers of Open Knowledge: A History of Open Access at IU Indianapolis
(2026-03-02) Molina, Rachel
This session talked about the history of open access at IU Indianapolis, beginning with the creation of one of the first institutional repositories in the state of Indiana and highlighting the major milestones reached since its inception.