Down-regulation of TGF-b1, TGF-b receptor 2, and TGF-b-associated microRNAs, miR-20a and miR-21, in skin lesions of sulfur mustard-exposed Iranian war veterans.
Sulfur mustard (SM) affects divergent cellular pathways including cell cycle, apoptosis, necrosis, and inflammatory responses. SM-induced lesions in skin include late-onset hyper-pigmentation, xerosis, and atrophy. It seems that TGF-b signaling pathway is a major player for SM pathogenesis. Here, we have employed a real-time polymerase chain reaction (PCR) approach to evaluate the expression alterations of all TGF-b variants and their receptors in skin biopsies obtained from 10 Iran-Iraq war veterans. Using specific LNA primers, the expression alteration of a TGF-bR2 regulator, miR-20a, and TGF-b downstream target, miR-21, was also assessed in the same samples Our real-time PCR data revealed a significant down-regulation of TGF-b1 and TGF-bR2, the major mediators of TGF-b signaling pathway, in skin biopsies of SM-exposed patients (p = 0.0015 and p = 0.0115, respectively). Down-regulation of TGF-b signaling pathway seems to contribute in severe inflammation observed in SM-exposed patients' tissues. MiR-20a and miR-21, as two important TGF-b associated microRNAs (miRNAs), were also down-regulated in SM-exposed skin lesions, compared to those of control group (p = 0.0003). Based on our findings, these miRNAs could be directly or indirectly involve in the pathogenesis of SM. Altogether, our data suggest the suitability of TGF-b1, TGF-bR2, as well as miR-20a and miR-21 as potential biomarkers for diagnosis and treatment of SM-exposed patients.
a Department of Genetics , Science and Research Branch Islamic Azad University , Tehran , Iran .|b ParsGenome Company , Tehran , Iran .
Mohadeseh
M
Valizadeh
a Department of Genetics , Science and Research Branch Islamic Azad University , Tehran , Iran .|b ParsGenome Company , Tehran , Iran .
Behnaz
B
Mirzaei
c Genetics Research Center, Baqyiatallah Medical Sciences University , Tehran , Iran .
Mahmood
M
Tavallaei
d Chemical Injuries Research Center, Baqiatallah University of Medical Sciences , Tehran , Iran .
Mohammad Reza
MR
Noorani
d Chemical Injuries Research Center, Baqiatallah University of Medical Sciences , Tehran , Iran .
Mojtaba
M
Amiri
e Janbazan Medical and Engineering Research Center (JMERC) , Tehran , Iran , and.
Mohammad Reza
MR
Soroush
f Faculty of Biological Sciences, Molecular Genetics Department , Tarbiat Modares University , Tehran , Iran.
Seyed Javad
SJ
Mowla
D000328:Adult; D016022:Case-Control Studies; D002619:Chemical Warfare Agents / Q000009:adverse effects*; D015536:Down-Regulation; D005260:Female; D006801:Humans; D007492:Iran / Q000453:epidemiology; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009151:Mustard Gas / Q000009:adverse effects*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics*; D012871:Skin Diseases / Q000139:chemically induced / Q000453:epidemiology / Q000235:genetics*; D053773:Transforming Growth Factor beta1 / Q000235:genetics*; D014728:Veterans; D014857:Warfare
D002619:Chemical Warfare Agents; C534451:MIRN20a microRNA, human; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D018125:Receptors, Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II; D009151:Mustard Gas
Gene expression; TGF-b; miR-20a; miR-21; skin; sulfur mustard