[Enhanced expression of signal transducers and activators of transcription in lung tissue of hypoxic pulmonary hypertension rat models].
OBJECTIVE
To investigate the expression levels of signal transducers and activators of transcription (STATs) in the lung tissue of hypoxic pulmonary hypertension (HPH) rat models.


METHODS
The Wister rat HPH models were divided into 4 groups: 1 week group (H1), 2 week group (H3), 3 week group (H3), and 4 week group (H4) (n = 12 in each group). The levels of STATsmRNA expression of the lung tissue were measured by reverse transcription-polymerase chain reaction (RT-PCR) and Northern blot. The protein expression of STATs and cellular morphologic changes were observed by immunohistochemistry and Tiger image analysis.


RESULTS
The RT-PCR showed that the levels of STAT1mRNA expression of the lung tissue in H1 1.25 +/- 0.12, H2 2.28 +/- 0.15 and H3 1.27 +/- 0.12 were significantly higher than that in the healthy control group 0.61 +/- 0.07 (P < 0.01); the levels of STAT2mRNA expression in H1 0.54 +/- 0.06, H2 1.01 +/- 0.08 and H3 1.36 +/- 0.09 were significantly higher than that in control group 0.30 +/- 0.03 (P < 0.01); the mRNA expressions of STAT3 in H1 0.74 +/- 0.11, H2 1.19 +/- 0.13 and H3 0.80 +/- 0.08 were significantly higher than that in control group 0.26 +/- 0.10 (P < 0.01); and the mRNA expressions of STAT5 in H1 0.92 +/- 0.10, H2 1.23 +/- 0.10 and H3 1.03 +/- 0.11 were significantly higher than that in control group 0.60 +/- 0.11 (P < 0.01). The Northern blot assay demonstrated that the expressions of STAT1mRNA in H1 0.49 +/- 0.10 and H3 0.67 +/- 0.07 were significantly different from that in H2 0.91 +/- 0.07 (P < 0.01); the expressions of STAT3mRNA in H1 2.10 +/- 0.21 and H3 2.58 +/- 0.17 were significantly different from that in H1 3.56 +/- 0.29 (P < 0.01); the expressions of STAT5mRNA in H1 0.99 +/- 0.10 and H3 1.45 +/- 0.12 were significantly different from that in H2 1.79 +/- 0.15 (P < 0.01). It is obvious that the mRNA expressions of STATs in the lung tissue of rat HPH models were increased in the 1st week, to the highest in the 2nd week, and decreased in the 3st week, and all higher than that of control group. The granules of STAT3 and STAT5, positively stained, were observed in the cytoplasm of pulmonary alveolar wall, intrapulmonary vascular and bronchial wall in H3. The protein expressions of STAT3 8.16 +/- 0.49 and STAT5 6.03 +/- 0.37 in H3 were markedly higher than those in H1, H4, and control group.


CONCLUSIONS
The up-regulation of the STATs expression in lung tissue of HPH rat models suggested that the STATs were involved in the pathogenesis of HPH formation.
Wang
Guan-song
GS
Institute of Respiratory Diseases, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.
Qian
Gui-sheng
GS
Bai
Li
L
Chen
Yan
Y
Wu
Guo-ming
GM
Zhou
De-shan
DS
Qian
Pin
P
D000818:Animals; D015152:Blotting, Northern; D004268:DNA-Binding Proteins / Q000032:analysis / Q000235:genetics*; D004195:Disease Models, Animal; D006976:Hypertension, Pulmonary / Q000378:metabolism*; D000860:Hypoxia / Q000378:metabolism*; D008297:Male; D008894:Milk Proteins; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor; D050799:STAT5 Transcription Factor; D015534:Trans-Activators / Q000032:analysis / Q000235:genetics*
D004268:DNA-Binding Proteins; D008894:Milk Proteins; D012333:RNA, Messenger; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor; D050799:STAT5 Transcription Factor; C494081:Stat1 protein, rat; C494088:Stat3 protein, rat; D015534:Trans-Activators