Pentraxin 3 inhibits acute renal injury-induced interstitial fibrosis through suppression of IL-6/Stat3 pathway.
Acute kidney injury-induced organ fibrosis is recognized as a major risk factor for the development of chronic kidney disease, which remains one of the leading causes of death in the developed world. However, knowledge on molecules that may suppress the fibrogenic response after injury is lacking. The long pentraxin 3 (PTX3), a novel acute renal injury marker, has been reported to be involved in chronic renal injury, but the mechanism is still unknown. In this experiment, the mice subjected to acute kidney injury showed a slow recovery of kidney function compared with PTX3-treated animals. Collagen expression was absent in sham-operated kidneys; however, their expression was significantly increased after reperfusion. And, these changes were reduced in PTX3-treated mouse kidney. Fibrosis was associated with increased expression of IL-6 and extensive activation of Stat3. Administration of IL-6 increased collagen I expression and Stat3 activation in vitro in renal epithelial cells subjected to hypoxia-reoxygenation, which was suppressed by PTX3. Furthermore, we found that the decreased serum creatinine level and the reduced expression of collagen and smooth muscle actin induced by PTX3 were abolished by additional administration of IL-6. The associated p-Stat3 expression which was reduced by PTX3 administration was also inverted by additional IL-6 treatment. Our data suggest that PTX3 inhibits acute renal injury-induced interstitial fibrosis through suppression of IL-6/Stat3 pathway.
Department of Nephrology, Aerospace Center Hospital, Aerospace Clinical Medical College, Peking University, No.15 Yuquan Road, Haidian District, Beijing, 100049, People's Republic of China, yuefeixiaobj@163.com.
Yuefei
Y
Xiao
Nainin
N
Yang
Qingxian
Q
Zhang
Yiping
Y
Wang
Songtao
S
Yang
Zhanxiao
Z
Liu
D058186:Acute Kidney Injury / Q000188:drug therapy* / Q000378:metabolism*; D000818:Animals; D002097:C-Reactive Protein / Q000494:pharmacology / Q000627:therapeutic use*; D002478:Cells, Cultured; D005355:Fibrosis / Q000188:drug therapy / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000683:Serum Amyloid P-Component / Q000494:pharmacology / Q000627:therapeutic use*; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D000099153:Pentraxins; D000093242:Interleukin-6 Inhibitors
D002097:C-Reactive Protein; D015850:Interleukin-6; D050796:STAT3 Transcription Factor; D000683:Serum Amyloid P-Component; D000099153:Pentraxins; D000093242:Interleukin-6 Inhibitors; C494087:Stat3 protein, mouse