Receptor for advanced glycation end‐products is a marker of type I lung alveolar cells

TLDR

Lung alveolar epithelium consists of type I (ATI) and type II (ATII) cells, with ATI cells being polarized yet extremely flat. The study aimed to identify membrane‑specific marker proteins for ATI cells, focusing on characterizing the receptor for advanced glycation end‑products (RAGE) as a potential marker. RAGE was characterized as a basolateral membrane marker of ATI cells through immunoelectron microscopy and expression analyses in vivo and in primary ATII‑derived cultures. RAGE localizes to basolateral membranes of ATI cells, its expression increases with ATI differentiation, co‑localizes with the apical marker T1α, and is induced only after T1α in vivo and ex vivo, confirming RAGE as a basolateral marker of well‑differentiated ATI cells that requires in‑vivo signals for expression.

Abstract

Lung alveolar epithelial cells are comprised of type I (ATI) and type II (ATII) cells. AΤΙ cells are polarized, although they have very flat morphology. The identification of marker proteins for apical and basolateral membranes of ATI cells is important to investigate into the differentiation of ATI cells. In this paper, we characterized receptor for advanced glycation end‐products (RAGE) as a marker for ATI cells. RAGE was localized on basolateral membranes of ATI cells in the immunoelectron microscopy and its expression was enhanced in a parallel manner to the differentiation of ATI cells in vivo and in primary cultures of ATII cells. RAGE and T1α, a well‐known ATI marker protein, were targeted to basolateral and apical membranes, respectively, when expressed in polarized Madine Darby canine kidney cells. Moreover, RAGE was expressed in ATI cells after T1α in vivo and in ex in vivo organ cultures. In conclusion, RAGE is a marker for basolateral membranes of well‐differentiated ATI cells. ATI cells require some signal provided by the in vivo environment to express RAGE.