Skip to Content
MilliporeSigma
  • Low molecular weight hyaluronan inhibits lung epithelial ion channels by activating the calcium-sensing receptor.

Low molecular weight hyaluronan inhibits lung epithelial ion channels by activating the calcium-sensing receptor.

Matrix biology : journal of the International Society for Matrix Biology (2023-02-10)
Ahmed Lazrak, Weifeng Song, Zhihong Yu, Shaoyan Zhang, Anoma Nellore, Charles W Hoopes, Bradford A Woodworth, Sadis Matalon
ABSTRACT

Herein, we tested the hypothesis that low molecular weight hyaluronan (LMW-HA) inhibits lung epithelial ions transport in-vivo, ex-vivo, and in-vitro by activating the calcium-sensing receptor (CaSR). Twenty-four hours post intranasal instillation of 50-150 µg/ml LMW-HA to C57BL/6 mice, there was a 75% inhibition of alveolar fluid clearance (AFC), a threefold increase in the epithelial lining fluid (ELF) depth, and a 20% increase in lung wet/dry (W/D) ratio. Incubation of human and mouse precision cut lung slices with 150 µg/ml LMW-HA reduced the activity and the open probability (Po) of epithelial sodium channel (ENaC) in alveolar epithelial type 2 (ATII) cells, and in mouse tracheal epithelial cells (MTEC) monolayers as early as 4 h. The Cl- current through cystic fibrosis transmembrane conductance regulator (CFTR) and the activity of Na,K-ATPase were both inhibited by more than 66% at 24 h. The inhibitory effects of LMW-HA on ion channels were reversed by 1 µM NPS-2143, or 150 µg/ml high molecular weight hyaluronan (HMW-HA). In HEK-293 cells expressing the calcium-sensitive Cl- channel TMEM16-A, CaSR was required for the activation of the Cl- current by LMW-HA. This is the first demonstration of lung ions and water transport inhibition by LMW-HA, and its mediation through the activation of CaSR.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
DAPT, ≥98% (HPLC), solid
Sigma-Aldrich
Anti-Calcium Sensing Receptor antibody, Mouse monoclonal, clone HL1499 (6D4-3F4-6C4), purified from hybridoma cell culture
Sigma-Aldrich
Anti-Actin, α-Smooth Muscle antibody, Mouse monoclonal, clone 1A4, purified from hybridoma cell culture