In the 1st funding period we proved that the extracellular matrix component (ECM) biglycan stimulates autophagy in macrophages by binding to CD44, thereby causing M2 macrophage polarization and kidney regeneration. Furthermore, we found that ABIN-1, a known regulator of macrophage polarization, interacts with mitophagy-related proteins and LC3B-II. In this project, we will decipher the mechanisms of ECM/CD44-dependent selective autophagy driving macrophage polarization and verify ABIN-1 as a new selective autophagy receptor to develop novel therapeutic activators of selective autophagy that prevent the progression of diabetic nephropathy.