Growth hormone induces mitotic catastrophe of glomerular podocytes and contributes to proteinuria

Abstract Glomerular podocytes are integral members of the glomerular filtration barrier in kidney and crucial for permselectivity. These highly differentiated cells vulnerable to an array noxious stimuli that prevail several diseases. Elevated circulating growth hormone (GH) levels associated with podocyte injury proteinuria diabetes. However, precise mechanism(s) by which excess GH elicits podocytopathy remains be elucidated. Previous studies have shown express receptor (GHR) induce Notch signaling when exposed GH. In present study, we demonstrated induces TGF-β1 provokes cell cycle reentry otherwise quiescent podocytes. Though reenter response TGF-β1, they cannot accomplish cytokinesis, despite karyokinesis. Owing this aberrant event, GH- or TGF-β1-treated remain binucleated undergo mitotic catastrophe. Importantly, inhibition JAK2, TGFBR1 (TGF-β 1), prevented protected them from catastrophe death. Inhibition activation prevents GH-dependent proteinuria. Similarly, attenuation GHR expression abated Kidney biopsy sections patients diabetic nephropathy (DN) show data indicate induced TGF-β1-dependent Notch1 contributes This study highlights role potential application inhibitors, as a therapeutic agent DN.