J WANG1, Q CAO1, Y WANG1, N ROGERS1, C POLLOCK2, P RAO1, V JAMES1, G ZHENG1, D HARRIS1, G ROBERTSON3, V LEE1
1Westmead Institute of Medical Research, Sydney, Australia, 2Kolling Institute of Medical Research, Sydney, Australia, 3Lyramid Ltd., Sydney, Australia
Aim: To examine Midkine (MK) expression and localisation in association with kidney injury and inflammatory features in murine models of acute and chronic kidney disease.
Background: Midkine (MK) is a growth factor which has been implicated as a pathological cytokine in experimental kidney disease, however its expression, localisation, and mechanisms of action during kidney injury remains unclear.
Methods: MK mRNA and protein expression and localisation were determined in various murine models of acute and chronic kidney disease, and correlated with kidney histopathological features, leukocyte infiltration, and chemokine expression.
Results: In normal mice, MK expression is localised to the glomeruli. In mice with Adriamycin nephropathy (AN), MK expression in kidney tissue was marginally increased at the mRNA level (p = 0.061), and markedly increased at the protein level by immunohistochemistry (p = 0.002) as compared to normal mice. In AN-induced mice, increased MK expression was found not only in the glomeruli, but also the tubules and tubulointerstitium. Circulating levels of MK remained unchanged in AN-induced mice relative to normal control mice (p = 0.870). MK protein expression in kidney tissue was positively correlated with progressive kidney injury (p < 0.001), while gene and protein expression were correlated with the number of infiltrating macrophages and T cells (p < 0.001), and expression of chemokines (p < 0.001). MK protein expression by immunohistochemistry was increased in mouse diabetic nephropathy, anti-glomerular basement membrane disease, and ischemic reperfusion injury as compared to control mice, and localised to the glomeruli, tubules or tubulointerstitium similar to AN.
Conclusions: These findings suggest that MK expressed by the kidney may be important to pro-inflammatory responses that mediate worsening kidney injury in experimental kidney disease.
I completed my Bachelor of Science degree with honours majoring in Biochemistry and Molecular and Cellular Biology at the University of Sydney, and the University of New South Wales. I am currently completing my PhD research degree in medicine, focusing on chronic kidney disease, with the University of Sydney. My primary background is biochemistry, molecular biology and immunology. To date I have publications in the field of nutrition, immunology, and clinical epidemiology.