Human Aquaporins: Functional Diversity and Potential Roles in Infectious and Non-infectious Diseases

Abstract

Aquaporins (AQPs) are integral membrane proteins and found in all living organisms from bacteria to human. AQPs mainly involved in the transmembrane diffusion of water as well as various small solutes in a bidirectional manner are widely distributed in various human tissues. Human contains 13 AQPs (AQP0–AQP12) which are divided into three sub-classes namely orthodox aquaporin (AQP0, 1, 2, 4, 5, 6, and 8), aquaglyceroporin (AQP3, 7, 9, and 10) and super or unorthodox aquaporin (AQP11 and 12) based on their pore selectivity. Human AQPs are functionally diverse, which are involved in wide variety of non-infectious diseases including cancer, renal dysfunction, neurological disorder, epilepsy, skin disease, metabolic syndrome, and even cardiac diseases. However, the association of AQPs with infectious diseases has not been fully evaluated. Several studies have unveiled that AQPs can be regulated by microbial and parasitic infections that suggest their involvement in microbial pathogenesis, inflammation-associated responses and AQP-mediated cell water homeostasis. This review mainly aims to shed light on the involvement of AQPs in infectious and non-infectious diseases and potential AQPs-target modulators. Furthermore, AQP structures, tissue-specific distributions and their physiological relevance, functional diversity and regulations have been discussed. Altogether, this review would be useful for further investigation of AQPs as a potential therapeutic target for treatment of infectious as well as non-infectious diseases.

Recent breakthroughs and future directions in drugging aquaporins

“…Thirteen aquaporin (see Glossary) isoforms are found throughout the human body, where they facilitate a range of functions including the secretion of cerebrospinal fluid (CSF), tears, saliva, sweat, and bile, and the concentration of urine (Table 1) [2]. Perturbation of aquaporin function can result in diverse disorders including loss of vision, loss of skin barrier function, kidney diseases, xerostomia (dry mouth), and the edema that follows stroke or trauma to the brain or spinal cord (Table 1) [2].…”

“…Thirteen aquaporin (see Glossary) isoforms are found throughout the human body, where they facilitate a range of functions including the secretion of cerebrospinal fluid (CSF), tears, saliva, sweat, and bile, and the concentration of urine (Table 1) [2]. Perturbation of aquaporin function can result in diverse disorders including loss of vision, loss of skin barrier function, kidney diseases, xerostomia (dry mouth), and the edema that follows stroke or trauma to the brain or spinal cord (Table 1) [2]. In the case of xerostomia (which is associated with reduced aquaporin 5 (AQP5) function in the salivary gland), pharmacological activation of AQP5 has been suggested as a treatment, either by direct channel agonism or by activation of a signaling pathway controlling AQP5 surface expression [3].…”

The Interplay between Histamine H4 Receptor and the Kidney Function: The Lesson from H4 Receptor Knockout Mice

“…The urine volume differences observed between wild-type and H4R -/-mice point out possible differences in the expression pattern of AQPs, a family of channel-forming transmembrane proteins differentially involved in water balance, included body water homeostasis [26]. Among them, AQP1, 3, and 7 are mainly expressed on the proximal tubular segment of the nephron.…”

Microbial Metabolites: The Emerging Hotspot of Antiviral Compounds as Potential Candidates to Avert Viral Pandemic Alike COVID-19

“…Despite the viral life cycle, a number of factors regulate the host response towards certain viral infections (Fung and Liu, 2019;Azad et al, 2021;Hakim et al, 2021). The inaugural stages of diseases include the viral phase with the appearance of symptoms.…”