Abstracts - Orals, Featured Poster Presentations, and Posters
MON 389-405-Signaling Originating from Membrane Receptors
Expo Halls ABC (Moscone Center)
Poster Board MON-399
Ischemia reperfusion injury (IRI) accompanies any organ transplant and can cause tissue damage leading to inflammation and fibrosis, a precursor to primary graft dysfunction. Since activin A is a major regulator of the inflammatory and fibrotic responses (1-3), we evaluated the changes in serum activin A (pg/ml) and its related protein activin B (pg/ml), both TFGβ related proteins, using specific ELISAs during the IRI response. Serum follistatin, an activin binding protein and a key regulator of activin bioactivity was measured by radioimmunoassay. Groups of unilaterally nephrectomised mice were subjected to renal ischemia for 20 mins by clamping of the renal pedicle of the remaining kidney, allowed to recover for 24 hrs before they were killed and blood was taken for measurements of the activins A & B, follistatin and serum creatinine (renal function marker). Groups of mice were killed prior to any procedure (basal n=7), after opening the abdomen and isolating but not clamping the renal vascular pedicle (sham n=4) and at 24 hrs post-renal artery clamping (n=8). All values are mean +/-sem. Serum creatinine in the baseline group (38.25 +/-1.0ng/ml) and sham treated group (28.75 +/-0.25) were unchanged but rose significantly at 24 hrs (103.3+/- 16.6; p<0.01).
There were increases between the basal and sham groups in both serum activin A (Base 67.6 +/- 13.6; Sham 103.4 +/- 14; pNS) and activin B (Base 664.9+/-91.8; Sham1232.4+/-8.3; p<0.002) and in these markers at 24hrs post-IRI (Serum act A 222.7+/- 15.6 p<0.001 sham versus 24hrs; Act B 4170.2+/-1061; Baseline versus 24hrs p<0.001). No significant changes were noted in the serum follistatin levels.
Although the increase between the basal and sham groups is significant for activin B but not activin A, the increases are likely to represent the acute phase response to surgery as shown previously for activin A and follistatin (3-5). The further increase in both activins at 24 hrs is related to the IRI, confirmed by the significant rise in serum creatinine resulting from the ischemic episode. In the absence of an increase in follistatin, these results raise the possibility that follistatin treatment may protect against the ischemic injury.
Disclosure: DD: Chief Scientific Officer, Paranta Biosciences. Nothing to Disclose: RO, MH, PC, KD
*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm
Sources of Research Support:
Support for this study was provided by a grant from the Cass Foundation. References: 1. Jones K et al Proc Natl Acad Sci 2007; 104:16239-44. 2. Aoki F et al Am J Resp Crit Care Med 2005; 172:713-20. 3. de Kretser DM et al Mol Cell Endocr 2012; 359:101-106. 4. Chen Y et al Cytokine 2011; 54:154-160. 5. Phillips DJ et al J Endocr 151;119-24.