Therefore, the elucidation of how various MAPs exert their effects on microtubules may have a profound impact on the diagnosis and therapy of many human diseases. Mdp3 has Epimedoside-A recently been characterized as a novel member of the MAP family. Intriguingly, Mdp3 interacts with microtubules/ tubulin and stabilizes microtubules through its amino-terminal region instead of its carboxyl-terminal MAP7 domain, indicating the structural diversity of the MAP7 domains present in different proteins. It would be interesting to investigate in the future whether the two closely related proteins, Mdp1 and Mdp2, interact with microtubules/tubulin and promote microtubule stability, and if so, whether these actions are mediated by their MAP7 domains. Further studies are also warranted to study the expression patterns of Mdp3 in different cell types and to analyze whether the expression or posttranslational modification of Mdp3 is altered in various human diseases. Stable microtubules are known to possess a high level of tubulin acetylation, although the causal relationship between tubulin acetylation and microtubule stability remains to be investigated. The acetyltransferases Elongator and MEC-17 have been reported to catalyze the tubulin acetylation process, and conversely the deacetylases HDAC6 and sirtuin 2 are able to remove the acetyl group from tubulin. The present study reveals that the amino-terminal region of Mdp3 mediates its interaction with HDAC6 in the cytoplasm, in addition to mediating Mdp3 binding to microtubules/tubulin. Interestingly, Mdp3 suppresses the activity of HDAC6, leading to enhanced tubulin acetylation. This finding suggests that Mdp3 might regulate microtubule stability by acting on HDAC6-mediated tubulin deacetylation, in addition to its direct association with microtubules/tubulin. HDAC6, as a unique member of the HDAC family with a predominant localization in the cytoplasm, has been implicated in numerous cellular processes such as cell motility, cell-cell interaction, and transcriptional regulation. HDAC6 carries out the above Gentiopicrin functions primarily through its deacetylation of substrate proteins such as a-tubulin, cortactin, and Hsp90. In addition, HDAC6 could interact with polyubiquitinated misfolded proteins and the dynein motor, facilitating the transport of misfolded proteins to the aggresome. Over the past decade, HDAC6 has emerged as a promising target for drug development due to its involvement in oncogenic cell transformation and neurodegeneration. In this scenario, our finding that Mdp3 is an endogenous inhibitor of HDAC6 may have important implications in health and diseases. The ACE2/Ang-/Mas axis is protective in renal disease, proven by the transgenic and knockout mouse models. However, the expression of ACE2 in diseased kidneys in previous studies is divergent. In addition, there are controversial data on the renoprotective effect of Ang-, including stimulation of inflammation by Ang-. Little is known about Mas receptor expression in CKD. Indoxyl sulfate, one of proteinbound uremic toxins, elicits a variety of cytotoxic effects, and exacerbates CKD. The role of IS on the Mas receptor has not been elucidated.