Determining the Role of Tubulointerstitial Nephritis Antigen-Like 1 in Renal Ischemic Reperfusion Injury

Abstract

Acute kidney injury (AKI) is a broad term that applies to a wide range of pathological etiologies characterized by a sudden increase in serum creatinine, a hallmark of malfunctioning kidneys. Ongoing efforts to elucidate the pathophysiology of AKI has shed light on certain proteins that may be involved during the kidney injury and repair process. One protein of interest is tubulointerstitial nephritis antigen like-1 (TINAGL1). In mice that has been subjected to renal ischemic reperfusion injury (IRI) surgery to induce AKI, mRNA transcripts of Tinagl1 has been found to be significantly increased shortly after AKI. We hypothesize that the upregulation of Tinagl1 plays an important role in mitigating the damage done by AKI and serve as an essential component during the process of repairing kidney tubules. In this study, we generated a mouse with Tinagl1 knockout and evaluated its susceptibility to renal tubular damage following IRI surgery. Results show that mice with knockout of Tinagl1 have far greater renal tubular damage compared to wild type littermates following kidney injury. Furthermore, we are able to demonstrate Tinagl1 is capable of potentiating Wnt signaling. Thus, our findings suggest Tinagl1 is a significant factor in mitigating kidney injury and can modulate the Wnt signaling pathway.