| First Author | Mukhi D | Year | 2023 |
| Journal | Biochim Biophys Acta Mol Cell Res | Volume | 1870 |
| Issue | 2 | Pages | 119391 |
| PubMed ID | 36400249 | Mgi Jnum | J:332200 |
| Mgi Id | MGI:7407822 | Doi | 10.1016/j.bbamcr.2022.119391 |
| Citation | Mukhi D, et al. (2022) Growth hormone induces transforming growth factor-beta1 in podocytes: Implications in podocytopathy and proteinuria. Biochim Biophys Acta Mol Cell Res 1870(2):119391 |
| abstractText | Pituitary growth hormone (GH) is essential for growth, metabolism, and renal function. Overactive GH signaling is associated with impaired kidney function. Glomerular podocytes, a key kidney cell type, play an indispensable role in the renal filtration and express GH receptors (GHR), suggesting the direct action of GH on these cells. However, the precise mechanism and the downstream signaling events by which GH leads to diabetic nephropathy remain to be elucidated. Here we performed proteome analysis of the condition media from human podocytes and confirmed that GH-induces TGF-beta1. Inhibition of GH/GHR stimulated-JAK2 signaling abrogates GH-induced TGF-beta1 secretion. Mice administered with GH showed glomerular manifestations concomitant with proteinuria. Pharmacological inhibition of TGF-betaR1 in mice prevented GH-induced TGF-beta dependent SMAD signaling and proteinuria. Conditional deletion of GHR in podocytes protected mice from streptozotocin-induced diabetic nephropathy. GH and TGF-beta1 signaling components expression was elevated in the kidneys of human diabetic nephropathy patients. Our study identifies that GH induces TGF-beta1 in podocytes, contributing to diabetic nephropathy. |
