Physiological Basis of Cystic Fibrosis: A Historical Perspective

Abstract

Physiological Basis of Cystic Fibrosis: A Historical Perspective. Physiol. Rev. 79, Suppl.: S3-S22, 1999. - Cystic fibrosis made a relatively late entry into medical physiology, although references to conditions probably reflecting the disease can be traced back well into the Middle Ages. This review begins with the origins of recognition of the symptoms of this genetic disease and proceeds to briefly review the early period of basic research into its cause. It then presents the two apparently distinct faces of cystic fibrosis: 1) as that of a mucus abnormality and 2) as that of defects in electrolyte transport. It considers principal findings of the organ and cell pathophysiology as well as some of the apparent conflicts and enigmas still current in understanding the disease process. It is written from the perspective of the author, whose career spans back to much of the initial endeavors to explain this fatal mutation.

Inhibitory Regulation of Cystic Fibrosis Transmembrane Conductance Regulator Anion-transporting Activities by Shank2

“…It is widely accepted that cAMP/PKA-induced phosphorylation performs critical roles in CFTR activation (23). To measure the levels of phosphorylation, 32 P labeling of CFTR protein was performed in NIH 3T3 cells (nominally in vivo phosphorylation assay) by stimulating with forskolin and treating with the phosphatase inhibitor NaVO 4 (Fig. 5C).…”

“…CFTR-Shank2 Interaction in Colonic Epithelia-Either hyper-or hypofunction of CFTR perturbs the epithelial homeostasis (4,5). Concerning the inhibitory regulation of Shank2 on CFTR, colonic epithelia will be the most relevant tissue to examine the physiological role of Shank2, where hyper-functioning of CFTR causes severe life-threatening conditions such as cholera (5,24).…”

“…One of the key membrane proteins regulating overall fluid movements is the cystic fibrosis transmembrane conductance regulator (CFTR), 1 which itself has an anion-transporting activity (1)(2)(3). Aberrant membrane transport caused by either hypo-or hyper-functioning of CFTR, can be detrimental, and may result in life-threatening diseases, such as cystic fibrosis or secretory diarrhea (4,5). Therefore, the fine regulation of salt and water transport is essential in epithelial and body homeostasis.…”

Relationships among CFTR expression, HCO 3 − secretion, and host defense may inform gene- and cell-based cystic fibrosis therapies

“…cystic fibrosis | gene therapy | host defense | pig | epithelia C ystic fibrosis (CF) is an autosomal recessive disease caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) (1)(2)(3). CFTR is an anion channel expressed in multiple cell types, including the apical membrane of airway epithelia.…”

Mechanisms of Bicarbonate Secretion: Lessons from the Airways

“…Adversely affected mucus leads to impaired mucociliary clearance from the submucosal glands and airway surface. The uncleared mucus then becomes a sink for bacterial binding, infection, and inflammation, thereby perpetuating a vicious cycle leading to further mucus secretion (Quinton 1999). This sequence of events is not restricted to the 40,000 individuals suffering from CF, but also occurs in more than 10 million patients suffering from COPD (chronic obstructive pulmonary disease) (Celli et al 1995;O'Byrine et al 1999).…”