Directed induction of alveolar type I cells derived from pluripotent stem cells via Wnt signaling inhibition

Oligohydramnios (OH) retards fetal lung growth by producing less lung distension than normal. To examine effects of decreased distension on fetal lung development, we produced OH in rats by puncture of uterus and fetal membranes at 16 days of gestation; fetuses were delivered at 21 or 22 days of gestation. Controls were position-matched littermates in the opposite uterine horn. OH lungs had lower weights and less DNA, protein, and water, but no differences in saturated phosphatidylcholine, surfactant proteins (SP)-A and -B, and mRNA for SP-A, -B, -C, and -D. To evaluate effects on epithelial differentiation, we used RTI40 and RTII70, proteins specific in lung to luminal surfaces of alveolar type I and II cells, respectively. At 22 days of gestation, OH lungs had less RTI40 mRNA ( P < 0.05) and protein ( P < 0.001), but RTII70 did not differ from controls. With OH, type I cells (in proportion to type II cells) covered less distal air space perimeter ( P < 0.01). We conclude that OH, which retards lung growth, has little effect on surfactant and impedes formation of type I cells relative to type II cells.

Download Full-text

UTP regulation of ion transport in alveolar epithelial cells involves distinct mechanisms

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.90268.2008 ◽

2009 ◽

Vol 297 (3) ◽

pp. L439-L454 ◽

Cited By ~ 7

Author(s):

Chuanxiu Yang ◽

Lijing Su ◽

Yang Wang ◽

Lin Liu

Keyword(s):

Ion Transport ◽

Short Circuit ◽

Alveolar Epithelial Cells ◽

Alveolar Type ◽

Channel Blockers ◽

Type I ◽

Type Ii Cells ◽

Type Ii ◽

Type I Cells ◽

I Cells

UTP is known to regulate alveolar fluid clearance. However, the relative contribution of alveolar type I cells and type II cells to this process is unknown. In this study, we investigated the effects of UTP on ion transport in type I-like cell (AEC I) and type II-like cell (AEC II) monolayers. Luminal treatment of cell monolayers with UTP increased short-circuit current ( Isc) of AEC II but decreased Isc of AEC I. The Cl− channel blockers NPPB and DIDS inhibited the UTP-induced changes in Isc (Δ Isc) in both types of cells. Amiloride, an inhibitor of epithelial Na+ channels (ENaC), abolished the UTP-induced Δ Isc in AEC I, but not in AEC II. The general blocker of K+ channels, BaCl2, eliminated the UTP-induced Δ Isc in AEC II, but not in AEC I. The intermediate conductance (IKCa) blocker, clofilium, also blocked the UTP effect in AEC II. The signal transduction pathways mediated by UTP were the same in AEC I and AEC II. Furthermore, UTP increased Cl− secretion in AEC II and Cl− absorption in AEC I. Our results suggest that UTP induces opposite changes in Isc in AEC I and AEC II, likely due to the reversed Cl− flux and different contributions of ENaC and IKCa. Our results further imply a new concept that type II cells contribute to UTP-induced fluid secretion and type I cells contribute to UTP-induced fluid absorption in alveoli.

Download Full-text