Calreticulin in renal fibrosis: A short review

Fibrosis is a common denominator of several pathological conditions. Over the last decade, Calreticulin has emerged as a critical player in the fibrotic processes in many tissues and organs. Here we review the recent advances in our understanding of the regulatory roles of Calreticulin in renal fibrosis. In particular, a proteomic screen that we performed more than 15 years ago, for the identification of novel components involved in the mechanisms of renal fibrosis, led to the observation that Calreticulin is associated with the initiation and progression of kidney fibrosis in a rodent model. We also showed that altered expression levels of Calreticulin in vitro and in vivo are significantly affecting the fibrotic phenotype in cellular systems and animal models, respectively. We also identified an upstream regulatory mechanism that mediates the transcriptional control of Calreticulin expression during the progression of renal fibrosis, by showing that the druggable orphan nuclear receptor NR5A2 and its SUMOylation is involved in this action. These data provide novel targets for future pharmacological interventions against fibrosis. In addition, further proteomic analysis uncovered a correlation between the up-regulation of Calreticulin and that of 14-3-3σ protein. Collectively, our previous observations suggest that Calreticulin is a central node in a regulatory axis that controls the initiation and progression of renal fibrosis.