Upregulation of Proapoptotic MicroRNA mir-125a After Massive Small Bowel Resection in Rats

• DOI: 10.1097/sla.0b013e31824b485a
• Publication Date: 2012-03-14T13:04:07Z
• Authors: Anita Balakrishnan; Adam T. Stearns; Peter J. Park; Jonathan M. Dreyfuss; Stanley W. Ashley; David B. Rhoads; Ali Tavakkolizadeh
• Keywords: Laser capture microdissection; Jejunum

Short bowel syndrome remains a condition of high morbidity and mortality, current therapeutic options carry significant side effects. To identify new treatments we focused on postresection changes in microRNAs--short noncoding RNAs, which suppress target genes--and suggest previously undiscovered role for microRNA-125a (mir-125a) intestinal adaptation.Rats underwent either 80% massive small resection or transection were harvested after 48 hours. Jejunum was microRNA microarrays, laser capture microdissection, RNA protein analysis. Mir-125a overexpressed epithelium-6 (crypt-derived) cells (IEC-6) effects proliferation apoptosis determined using MTS flow cytometry. Expression potential targets mir-125a rat jejunum IEC-6 quantitative real-time polymerase chain reaction (RNA) Western blotting (protein).Resection upregulated mir-214 by 2.4-folds 3.2-folds, respectively. Highest levels expression noted the crypt fraction. overexpression induced resultant growth arrest cells. The prosurvival Bcl-2 family member Mcl-1 downregulated both mir-125a-overexpressing resected rats, confirming as mir-125a.Upregulation suppresses Mcl1, producing increase known to accompany proliferative characteristic adaptation. Our data highlight microRNAs mediators adaptive process may facilitate development short syndrome.