Krüppel-like zinc finger proteins in end-stage COPD lungs with and without severe alpha1-antitrypsin deficiency

Abstract

BackgroundChronic obstructive pulmonary disease (COPD) is influenced by environmental and genetic factors. An important fraction of COPD cases harbor a major genetic determinant, inherited ZZ (Glu342Lys) α1-antitrypsin deficiency (AATD). A study was undertaken to investigate gene expression patterns in end-stage COPD lungs from patients with and without AATD.MethodsExplanted lungs of end-stage ZZ AATD-related (treated and non-treated with AAT augmentation therapy) and “normal” MM COPD, and liver biopsies from patients suffering from liver cirrhosis with and without ZZ AATD were used for gene expression analysis by Affymetrix microarrays or RT-PCR.ResultsA total of 162 genes were found to be differentially expressed (p-value ≤ 0.05 and |FC| ≥ 2) between MM and ZZ COPD patients. Of those, 134 gene sets were up-regulated and 28 were down-regulated in ZZ relative to MM lung tissue. A subgroup of genes, zinc finger protein 165, snail homolog 1 (Drosophila) (SNAI1), and Krüppel-like transcription factors (KLFs) 4 (gut), 9 and 10, perfectly segregated ZZ and MM COPD patients. The higher expression of KLF 9 and KLF10 has been verified in the replication cohort with AATD-related end-stage lung emphysema and liver cirrhosis. Furthermore, higher expression of KLF9, SNAI1 and DEFA1 was found in ZZ COPD lungs without augmentation therapy relative to MM COPD or ZZ COPD with augmentation therapy.ConclusionsThese results reveal the involvement of transcriptional regulators of the zinc-finger family in COPD pathogenesis and provide deeper insight into the pathophysiological mechanisms of COPD with and without AATD.

The molecular mechanism study of insulin on proliferation and differentiation of osteoblasts under high glucose conditions

“…Moreover, three differentially expressed mRNAs including up‐regulated Krüppel‐like factor 10 (Klf10) and down‐regulated paired box 8 (Pax8) and PR/SET domain 16 (Prdm16) were included in these processes. KLF10 (also called EGR‐alpha, EGRA, TIEG, and TIEG1) is a member of the Krüppel family of transcription factors and plays various roles in cell proliferation, differentiation, bone formation, and mineralization in human osteoblasts . It is indicated that deletion of KLF10 in osteoblasts leads to disorders of canonical and noncanonical Wnt signalling pathways during the course of osteoblasts differentiation .…”

“…25 osteoblasts. 21,26 It is indicated that deletion of KLF10 in osteoblasts leads to disorders of canonical and noncanonical Wnt signalling pathways during the course of osteoblasts differentiation. 27 PAX8, a tissue-specific transcription factor, belongs to the Pairedbox (Pax) gene family.…”

Krüppel-like factor KLF10 deficiency predisposes to colitis through colonic macrophage dysregulation

“…Recent report also suggested KLF10 as a susceptibility gene for IgA nephropathy in Han Chinese (17). Higher levels of KLF10 have also been described in human chronic obstructive pulmonary disease and liver cirrhosis (14). There is no known effect of low KLF10 that may affect innate immune response in human disease.…”

KLF10 as a Tumor Suppressor Gene and Its TGF-β Signaling

“…This up-regulation of KLF10 increased TGF-β signaling genes and suppressed ChREBP expression [ 40 ]. Furthermore, KLF10 plays a role in hyperglycemia [ 55 ], human chronic obstructive pulmonary diseases and liver cirrhosis [ 56 ], tendon repair [ 57 ], and hypoxia [ 58 ]. However, the actual functional role and mechanism of KLF10 in various pathophysiological conditions are still uncertain.…”