Legumain, an asparaginyl endopeptidase, mediates the effect of M2 macrophages on attenuating renal interstitial fibrosis in obstructive nephropathy

Legumain is upregulated in acute cardiovascular events and associated with improved outcome - potentially related to anti-inflammatory effects on macrophages

“…This may be contradictory to the suggested detrimental role in inflammation and ECM remodeling, but there are also data suggesting a role for legumain in tissue repair [23]. Moreover, in an experimental mouse model legumain was shown to mediate anti-inflammatory and pro-resolving effects of M2 macrophages by attenuating renal interstitial fibrosis in obstructive nephropathy [24]. Indeed, the present study indicates that legumain induces polarization of anti-inflammatory macrophages, shown by an upregulation of several genes such as CD163, which could potentially reflect polarization of monocytes towards the M2 phenotype, while downregulating a M1 phenotype.…”

Petchiether A attenuates obstructive nephropathy by suppressing TGF‐β/Smad3 and NF‐κB signalling

“…Findings from other research teams indicate that TGF-β1 activates renal tubular cells and immune system cells to produce inflammatory cytokines and further promote the inflammatory response, which, in turn, amplifies fibrosis and tubular injury. [47][48][49] The mechanisms by which petA attenuates inflammation will be explored in future studies.…”

Glycosylation is important for legumain localization and processing to active forms but not for cystatin E/M inhibitory functions

“…Legumain has previously been suggested to play a role in tissue repair [290]. Moreover, in data from an experimental mouse model, legumain was shown to mediate anti-inflammatory and pro-resolving effects of M2 macrophages by attenuating renal interstitial fibrosis in obstructive nephropathy [291].…”

“…LSAM can also function as a direct stabilizer of the catalytic domain by physically protection in a neutral pH environment [27]. Recently, legumain has been found in exosomes derived from M2 macrophages [43]. Extracellular legumain is internalized by cells and subsequently processed and activated [44].…”