Premium
Role of Krüppel Like Factor (Klf4) in Pulmonary Fibrosis
Author(s) -
Perkins Tina,
Wary Kishore
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.625.1
Subject(s) - klf4 , offspring , lung , biology , endocrinology , chemistry , medicine , biochemistry , transcription factor , pregnancy , sox2 , genetics , gene
Rationale The mature endothelial cells (ECs) encounter with and must respond to several ‘intrinsic’ and ‘extrinsic’ endothelial disrupting factors and inflammatory cytokines. In this regard, KLF4 has been suggested to play an EC protective role; however, the underlying mechanisms are poorly understood. Goal To address the role of Klf4 in adult lung microvessels by deleting EC‐ Klf4 in a timed manner. Methods and Results Immunostaining showed significant reduction of KLF4 expression in human emphysema lung tissue samples. Cigarette smoke condensate decreased expression of KLF4 in ECs. Therefore, to address the role EC‐Klf4 in mice, male Klf4 fl/+ were crossed with female Klf4 fl/+ mice to generate Klf4 fl/fl (25%)offspring. Next, Klf4 fl/fl mice were crossed with male tg‐ Cdh5 CreERT2 mice to produce heterozygous Klf4 fl ::tg‐ Cdh5 CreERT2 offspring (100%). Thereafter, male Klf4 fl ::tg‐Cdh5 CreERT2 were crossed with female Klf4 fl ::tg‐ Cdh5 CreERT2 to produce Klf4 fl/fl ::tg‐ Cdh5 CreERT2 siblings (25%). Groups of these mice received tamoxifen (TAM) everyday for 5 days, and on the 10 th day (called Klf4 ECKO mice) were sacrificed. Accordingly, TAM treatment decreased EC‐Klf4‐protein expression significantly in the Klf4 ECKO lug compared to Klf4 fl/fl ortg‐ Cdh5 CreERT2 controls. Klf4 ECKO lung tissue showed increased recruitment of neutrophils and inflammatory cells. Trichrome staining revealed increased collagen deposition in the Klf4 ECKO versus wild‐type mice. Importantly, the number of lung alveoli decreased (p<0.05 vs control, n=5), hemorrhage in Klf4 ECKO mice compared to the control. Accordingly, the number of CD31+ vascular structures decreased in these mice. Summary Klf4 protect ECs from ‘intrinsic’ and ‘extrinsic’ endothelial disrupting factors, therefore its loss results in pulmonary fibrosis.