Fig. 5: TM4SF5 expression was critical for AECII survival during bleomycin-induced pulmonary fibrosis. | Cell Death & Disease

Fig. 5: TM4SF5 expression was critical for AECII survival during bleomycin-induced pulmonary fibrosis.

From: TM4SF5-mediated CD44v8-10 splicing variant promotes survival of type II alveolar epithelial cells during idiopathic pulmonary fibrosis

Fig. 5

a, b Lung tissues from control saline or bleomycin-treated wild-type (WT) or Tm4sf5−/−-knockout mice were analyzed for collagen levels by Masson Trichrome staining (a), immunohistochemistry for α-SMA and fibronectin (b), or hydroxyproline analysis (c). d The survival rates were plotted for WT or Tm4sf5−/− mice treated with either control saline or bleomycin. e, f AECI or AECII cultures were prepared from WT mice and analyzed for AEC biomarkers (e) and Tm4sf5-related mRNAs (f). g, h Primary AECI or AECII cells were prepared from lung tissues of WT or Tm4sf5−/− mice and processed for qRT-PCR (g) or western blot analyses (h). i The primary cells in (g) were treated with control vehicle or TNF-α, followed by DCF-DA staining for ROS. Data represent three isolated experiments. j The mechanistic working model. Elevated TM4SF5 expression leads to lower ZEB2 and higher splicing factor ESRP1/2 levels, leading to induction of alternative splicing variant CD44v8-10, which replaces the CD44s form. TM4SF5 and the TM4SF5-induced CD44v8-10 variant form a protein complex along with CD98hc and xCT for cystine uptake and glutamate secretion. This leads increased intracellular GSH levels for hormetic regulation of intracellular ROS levels and eventual survival or protection of AECII from cytotoxic ROS stimuli, such as serum starvation, TNF-α treatment, or NOX2/NOX4 expression

Back to article page