# Sorcin regulates alveolarization and airway tissue remodeling during lung morphogenesis

## TL;DR

This study shows that Sorcin, a calcium-sensing protein, plays a key role in lung development and airway structure, with its absence leading to impaired alveolarization and surfactant production.

## Contribution

The study reveals a novel role for Sorcin in regulating lung morphogenesis and surfactant production through its interaction with EGFR signaling.

## Key findings

- Sorcin knockout mice show impaired alveolarization and abnormal bronchial development.
- Sorcin deficiency leads to reduced expression of branching morphogenesis and surfactant protein genes.
- Sorcin knockout mice exhibit increased bronchial thickening and airway remodeling.

## Abstract

Sorcin, a key calcium-sensing protein, regulates calcium concentration within the endoplasmic reticulum (ER), promoting apoptosis resistance and ER stress. It also modulates downstream signaling pathways of the epidermal growth factor receptor (EGFR), influencing cellular migration and invasion in non-small-cell lung carcinoma (NSCLC) cell lines. For this purpose, this study investigates the relationship between Sorcin and EGFR expression during lung development at the physiological level. Our study was conducted on WT and Sorcin Knock-out (Sri−/−) mice, where we performed various analyses, including histological examination, gene and protein expression analysis, and confocal microscopy. Our findings reveal that Sri−/− mice, compared to wild-type controls, exhibit: (1) impaired alveolarization and abnormal development of bronchi and bronchioles, as observed in histological sections; (2) decreased expression of genes encoding branching morphogenesis markers (e.g., Fgf10) and surfactant proteins (e.g., Sp-b, Sp-c and Abca3), as shown by real-time PCR; (3) increased glycogen content decreased lipid droplets, indicative of type II pneumocyte immaturity and impaired surfactant lipid production; (4) reduced levels of EGFR, RAS and RAB5C proteins, consistent with defects in lung maturation and surfactant protein recycling, as demonstrated by Western blot analysis; and (5) increased expression of phalloidin, α-smooth muscle actin and vimentin, suggesting increased bronchial thickening associated with airway tissue remodeling. Collectively, these data reveal a novel role for Sorcin in lung alveolarization, pulmonary surfactant production, and airway remodeling associated with bronchial contractility, supporting its involvement in respiratory diseases such as respiratory distress syndrome (RDS), asthma and chronic obstructive pulmonary disease (COPD).

The online version contains supplementary material available at 10.1007/s00018-025-05870-y.