Transforming growth factor-beta isoforms and glomerular injury in nephrotoxic nephritis
Related Experiment Video
Updated: Oct 16, 2026

Identification of the Source of Secreted Proteins in the Kidney by Brefeldin A Injection
Published on: November 10, 2021
H M Wilson1, A W Minto, P A Brown
1Department of Medicine and Therapeutics, University of Aberdeen, Aberdeen, Scotland, United Kingdom. h.m.wilson@abdn.ac.uk
Background:
Transforming growth factor-beta has three main isoforms (TGF-beta1, TGF-beta2, and TGF-beta3) that have distinct but overlapping functions in immunity, inflammation, and tissue repair. TGF-beta1 has been implicated in progressive renal scarring, but the roles of TGF-beta2 and TGF-beta3 are less clear. The purpose of this study was to characterize the expression of all three isoforms in nephrotoxic nephritis (NTN) in rats and to determine the effect of TGF-beta3 infusions on injury because of its reported combined anti-inflammatory and antifibrotic effects.
Methods:
TGF-beta1, TGF-beta2, and TGF-beta3 expression was analyzed by immunohistochemistry and RNase protection assays. TGF-beta3 was administered by osmotic minipumps at 2 microg/day, a dose shown to alter glomerular macrophage function in vivo. Injury was assessed morphologically and functionally.
Results:
The three TGF-beta isoforms showed a different distribution in normal rats and after the induction of nephritis. TGF-beta1 was only detected in glomeruli of the most severely nephritic rats. TGF-beta2 was found in glomerular neutrophils, whereas damaged podocytes expressed TGF-beta3. Infusions of TGF-beta3 did not reduce proteinuria over seven days after the induction of nephritis. They did, however, have a profound effect on glomerular macrophage number (7.76 +/- 4.1 in treated rats vs. 14.4 +/- 4.7 in controls, P < 0.02). The numbers of class II-positive macrophages were similar in the two groups, whereas class II-negative macrophages infiltrating glomeruli were significantly decreased (4.06 +/- 3.1 vs. 9.1 +/- 4.4, P < 0.02). TGF-beta did not influence the amount of glomerular matrix.
Conclusions:
TGF-beta isoforms have different expressions and presumptively different roles in NTN. The infusion of pharmacological doses of TGF-beta3 has profound effects on macrophages infiltrating nephritic glomeruli and reveals marked heterogeneity of infiltrating macrophages.
Related Concept Videos
Acute Kidney Injury II: Pathophysiology
TGF - β Signaling Pathway
Nephrotic Syndrome I : Introduction
Glomerular Filtration Rate and its Regulation
GFR regulation involves two primary intrinsic controls: the myogenic and tubuloglomerular feedback mechanisms.
The myogenic...
Renal Corpuscle
Glomerulus: Structure and Function
The glomerulus is a tiny, intricate network of capillaries located at the beginning of the nephron. It's enveloped by the Bowman's capsule and receives its blood supply from an afferent arteriole, which divides into numerous capillaries...
Enzyme-linked Receptors