Pyrintegrin, a β1-integrin agonist, promotes the survival of embryonic stem cells, can be used as a podocyte-protective agent, and enhances cell-extracellular matrix adhesion-mediated integrin signaling.

Pyrintegrin decreases Runx2 and Osx via BMP-mediated SMAD1/5 phosphorylation. Pyrintegrin treatment prevents damage-induced decreases in F-actin stress fibers, focal adhesions, and active β1-integrin levels in cultured cells. Pyrintegrin stimulates human adipose stem/progenitor cells (hASCs) to differentiate into lipid-laden adipocytes by upregulating peroxisome proliferator-activated receptor (PPARγ) and CCAAT/enhancer-binding protein-α (C/EBPα), with differentiated cells increasingly secreting adiponectin, leptin, glycerol, and total triglycerides. Pyrintegrin (0-10 μM; 1 hour; hASCs) treatment inhibits BMP4-mediated phosphorylation of BMP responsive SMAD1/5 in a dose-dependent manner (IC50 of 1.14 μM) [1][2].

Pyrintegrin induces postnatal adipose tissue formation in vivo of transplanted adipose stem/progenitor cells (ASCs) and recruited endogenous cells. Pyrintegrin decreases peak proteinuria caused by puromycin aminonucleoside-induced nephropathy. Pyrintegrin-treated human adipose stem/progenitor cells (ASCs) in 3D-bioprinted scaffolds, when transplanted in the dorsum of athymic mice, yielded ectopically formed adipose tissue that expressed human PPARγ. Pyrintegrin-adsorbed collagen gel implanted in the inguinal fat pad promoted adipogenesis formed by host endogenous cells, suggesting its ability to induce in situ adipogenesis without the need for cell transplantation. Pyrintegrin (10 mg/kg; intraperitoneal injection; once; C57BL/6J mice) treatment protects mice from LPS-induced podocyte foot process effacement and proteinuria. LPS administration decreases the levels of active β1 integrin in the podocytes, which is prevented by cotreatment with Pyrintegrin [1][2].