Protective Role of Tangshen Formula on the Progression of Renal Damage indb/dbMice by TRPC6/Talin1 Pathway in Podocytes

Abstract

Tangshen Formula (TSF) is a Chinese Medicine formula that has been reported to alleviate proteinuria and protect renal function in humans and animals with diabetic kidney disease (DKD). However, little is known about its mechanism in improving proteinuria. The dysregulation of podocyte cell-matrix adhesion has been demonstrated to play an important role in the pathogenesis and progression of proteinuric kidney diseases including DKD. In the present study, the underlying protective mechanism of TSF on podocytes was investigated using the murine model of type 2 DKD db/db mice in vivo and advanced glycation end products (AGEs)-stimulated primary mice podocytes in vitro. Results revealed that TSF treatment could significantly mitigate reduction of podocyte numbers and foot process effacement, reduce proteinuria, and protect renal function in db/db mice. There was a significant increase in expression of transient receptor potential canonical channel 6 (TRPC6) and a decrease in expression of talin1 in podocytes of db/db mice. The results of AGEs-stimulated primary mice podocytes showed increased cell migration and actin-cytoskeleton rearrangement. Moreover, primary mice podocytes stimulated by AGEs displayed an increase in TRPC6-dependent Ca2+ influx, a loss of talin1, and translocation of nuclear factor of activated T cell (NFATC) 2. These dysregulations in mice primary podocytes stimulated by AGEs could be significantly attenuated after TSF treatment. 1-Oleoyl-2-acetyl-sn-glycerol (OAG), a TRPC6 agonist, blocked the protective role of TSF on podocyte cell-matrix adherence. In conclusion, TSF could protect podocytes from injury and reduce proteinuria in DKD, which may be mediated by the regulation of the TRPC6/Talin1 pathway in podocytes.

Fufang shenhua tablet, astragali radix and its active component astragaloside IV: Research progress on anti-inflammatory and immunomodulatory mechanisms in the kidney

“…Podocytes represent a specialized subtype of differentiated epithelial cells that are responsible for upholding the structural and functional integrity of the glomerular filtration barrier, and furthermore determine the size of filtration proteins. When podocytes undergo apoptosis and are consequently lost, the filtration barrier structure collapses, which in turn leads to proteinuria ( Lin et al, 2020 ; Wang et al, 2020 ).…”

High-sulfated derivative of polysaccharide fromUlva pertusaimproves Adriamycin-induced nephrotic syndrome by suppressing oxidative stress

“…Images were observed under a light microscope and processed with Image-Pro Plus 6.0 software. 31 For immunofluorescence, paraffin-embedded kidneys were cut into 2 µm sections, and were incubated in 5% BSA to block for 1 hour at room temperature and stained with anti-Nrf2 antibody (1 : 50) and secondary antibody CoraLite594-conjugated goat anti-rabbit (1 : 200). Images were then obtained by a fluorescent inverted microscope (Olympus).…”

Neurons: The Interplay between Cytoskeleton, Ion Channels/Transporters and Mitochondria

“…Another example is given by voltage-gated calcium channels: actin cytoskeleton participates in the crosstalk of L-type of these channels and mitochondria, obtaining a regulation of noradrenergic activity in the locus coeruleus, a fundamental relationship for integrative brain functions [ 69 ]. Transient receptor potential (TRP) cation channels, which are involved in Ca2+ signaling, also have a peculiar relationship with the cytoskeleton which might act as a modulator of TRP, but are modulated by TRP via a downstream effect of TRP function [ 70 ]. Therefore, the cytoskeleton, and actin in particular, may represent a underrecognized mechanism of modulation and activation of voltage-gated and non-voltage-gated ion channels in neurons [ 45 ].…”