Pentraxin 3 Inhibits Acute Renal Injury-Induced Interstitial Fibrosis Through Suppression of IL-6/Stat3 Pathway

Abstract

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.

Pentraxins in the activation and regulation of innate immunity

“…A role for PTX3 is described in different models of ischemia and reperfusion. In a model of postischemic renal injury, ptx3 −/− mice showed increased tissue damage and administration of recombinant protein exerted a protective effect, with enhanced recovery, suppression of glomerulal sclerosis, and inhibition of interstitial fibrosis . Interaction between PTX3 and P‐selectin also plays a role in this model.…”

Association of Serum Pentraxin 3 Concentrations with Diabetic Nephropathy

“…Furthermore, renal leukocyte recruitment and postischemic kidney injury were improved with PTX3 treatment after reperfusion 20. In another study performed in mice, PTX3 treatment inhibited acute renal injury-induced interstitial fibrosis, and resulted in decreased serum creatinine level and reduced expression of collagen and smooth muscle actin 21. In addition, PTX3 was found to attenuate renal damage by promoting M2 macrophage differentiation in mice model of hyperglycemia-induced nephropathy 10.…”

Pentraxins and Collectins: Friend or Foe during Pathogen Invasion?

“…In summary, the multifunctional characteristics of PTX3 can give rise to protective or pathogenic effects in response to different pathogen-induced inflammation. In a context of sterile inflammation, such as in tissue injury mediated by ischaemia and reperfusion, PTX3 can be protective (e.g., kidney) or deleterious (e.g., intestine), depending on the tissue [52,53]. PTX3 is endowed with a strong immunomodulatory role which can have a diverse impact on downstream innate immune responses, strongly suggestive of its therapeutic potential.…”