Endolyn/CD164 Regulates Proximal Tubule Cell Survival

Abstract

Endolyn/CD164 is a sialomucin expressed in epithelial, hematopoietic, and several other cell types. CD164 has been implicated in proliferation, adhesion, and migration of both normal and cancer cells. In proximal straight and distal tubules and in the collecting system, CD164 primarily localizes to endosomes and lysosomes; however, in proximal convoluted tubules, a significant fraction of CD164 localizes to the brush border. In mouse models of ischemia reperfusion injury the majority of surviving proximal tubule cells (PT) sustain sublethal injury due to oxygen and nutrient deprivation. Studies suggest that PT cells could undergo a number of cellular processes, such as autophagy, dedifferentiation, and proliferation in order to restore nephron function. Recently, the process of autophagy has drawn attention as having a possible role in PT cell repair. Interestingly, we found that CD164 expression is upregulated in PT cells of rat kidney after ischemia reperfusion injury. We hypothesize that PT cells upregulate CD164 expression to trigger cell survival mechanisms like autophagy after ischemia-reperfusion injury. To investigate the mechanisms involved in regulation and function of CD164, we treated immortalized mouse PT cells with siRNA targeting CD164. The decreased CD164 expression resulted in diminished cell numbers, cells with a more elongated morphology, and cells with enlarged lysosomes as measured by indirect immunofluorescence. When apoptosis was measured by flow cytometry, CD164 knockdown increased the number of cells in early and late apoptosis compared to control cells. In conclusion, CD164 may play a critical role in PT cell survival by contributing to proper lysosomal distribution and function. This research was supported by AHA 12SDG12040003.