{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T01:44:34Z","timestamp":1790905474510,"version":"4.1.0"},"reference-count":55,"publisher":"National Academy of Sciences","issue":"14","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2000,7,5]]},"abstract":"<jats:p>\n                    Emerging evidence suggests that transforming growth factor-\u03b2 (TGF-\u03b2) is an important mediator of diabetic nephropathy. We showed previously that short-term treatment with a neutralizing monoclonal anti-TGF-\u03b2 antibody (\u03b1T) in streptozotocin-diabetic mice prevents early changes of renal hypertrophy and increased matrix mRNA. To establish that overactivity of the renal TGF-\u03b2 system mediates the functional and structural changes of the more advanced stages of nephropathy, we tested whether chronic administration of \u03b1T prevents renal insufficiency and glomerulosclerosis in the\n                    <jats:italic>db\/db<\/jats:italic>\n                    mouse, a model of type 2 diabetes that develops overt nephropathy. Diabetic\n                    <jats:italic>db\/db<\/jats:italic>\n                    mice and nondiabetic\n                    <jats:italic>db\/m<\/jats:italic>\n                    littermates were treated intraperitoneally with \u03b1T or control IgG, 300 \u03bcg three times per week for 8 wk. Treatment with \u03b1T, but not with IgG, significantly decreased the plasma TGF-\u03b21 concentration without decreasing the plasma glucose concentration. The IgG-treated\n                    <jats:italic>db\/db<\/jats:italic>\n                    mice developed albuminuria, renal insufficiency, and glomerular mesangial matrix expansion associated with increased renal mRNAs encoding \u03b11(IV) collagen and fibronectin. On the other hand, treatment with \u03b1T completely prevented the increase in plasma creatinine concentration, the decrease in urinary creatinine clearance, and the expansion of mesangial matrix in\n                    <jats:italic>db\/db<\/jats:italic>\n                    mice. The increase in renal matrix mRNAs was substantially attenuated, but the excretion of urinary albumin factored for creatinine clearance was not significantly affected by \u03b1T treatment. We conclude that chronic inhibition of the biologic actions of TGF-\u03b2 with a neutralizing monoclonal antibody in\n                    <jats:italic>db\/db<\/jats:italic>\n                    mice prevents the glomerulosclerosis and renal insufficiency resulting from type 2 diabetes.\n                  <\/jats:p>","DOI":"10.1073\/pnas.120055097","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:37:36Z","timestamp":1027679856000},"page":"8015-8020","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":716,"title":["Long-term prevention of renal insufficiency, excess matrix gene expression, and glomerular mesangial matrix expansion by treatment with monoclonal antitransforming growth factor-\u03b2 antibody in\n                    <i>db\/db<\/i>\n                    diabetic mice"],"prefix":"10.1073","volume":"97","author":[{"given":"Fuad N.","family":"Ziyadeh","sequence":"first","affiliation":[{"name":"Renal-Electrolyte and Hypertension Division, University of Pennsylvania, Philadelphia, PA 19104-6144; and Division of Nephrology, Thomas Jefferson University, Philadelphia, PA 19107"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brenda B.","family":"Hoffman","sequence":"additional","affiliation":[{"name":"Renal-Electrolyte and Hypertension Division, University of Pennsylvania, Philadelphia, PA 19104-6144; and Division of Nephrology, Thomas Jefferson University, Philadelphia, PA 19107"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong Cheol","family":"Han","sequence":"additional","affiliation":[{"name":"Renal-Electrolyte and Hypertension Division, University of Pennsylvania, Philadelphia, PA 19104-6144; and Division of Nephrology, Thomas Jefferson University, Philadelphia, PA 19107"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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