Abstract
Carbon dioxide (CO2) is produced in eukaryotic cells primarily during aerobic respiration, resulting in higher CO2 levels in mammalian tissues than those in the atmosphere. CO2 like other gaseous molecules such as oxygen and nitric oxide, is sensed by cells and contributes to cellular and organismal physiology. In humans, elevation of CO2 levels in tissues and the bloodstream (hypercapnia) occurs during impaired alveolar gas exchange in patients with severe acute and chronic lung diseases. Advances in understanding of the biology of high CO2 effects reveal that the changes in CO2 levels are sensed in cells resulting in specific tissue responses. There is accumulating evidence on the transcriptional response to elevated CO2 levels that alters gene expression and activates signaling pathways with consequences for cellular and tissue functions. The nature of hypercapnia-responsive transcriptional regulation is an emerging area of research, as the responses to hypercapnia in different cell types, tissues, and species are not fully understood. Here, we review the current understanding of hypercapnia effects on gene transcription and consequent cellular and tissue functions.
Highlights
Cells and tissues possess the ability to sense and respond to alterations in the concentration of gaseous molecules
We review recent advances in our understanding of hypercapnia-regulated gene transcription and consequent cellular/tissue functions focusing on lung and skeletal muscle functions and innate immune system
Persistent hypercapnia is associated with increased disease severity and worse prognosis in obstructive lung diseases such as obesity hypoventilation syndrome (Piper, 2015) and chronic obstructive pulmonary disease (COPD) (Connors et al, 1996; Köhnlein et al, 2014; Murphy et al, 2017)
Summary
Division of Pulmonary and Critical Care Medicine, Northwestern University, Chicago, IL, United States. Reviewed by: Vincent Joseph, Laval University, Canada Matt Robert Hodges, Medical College of Wisconsin, United States Cormac Taylor, University College Dublin, Ireland. Advances in understanding of the biology of high CO2 effects reveal that the changes in CO2 levels are sensed in cells resulting in specific tissue responses. There is accumulating evidence on the transcriptional response to elevated CO2 levels that alters gene expression and activates signaling pathways with consequences for cellular and tissue functions. The nature of hypercapnia-responsive transcriptional regulation is an emerging area of research, as the responses to hypercapnia in different cell types, tissues, and species are not fully understood. We review the current understanding of hypercapnia effects on gene transcription and consequent cellular and tissue functions
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