Glomerular parietal epithelial cell activation induces collagen secretion and thickening of Bowman's capsule in diabetes

TY - JOUR

T1 - Glomerular parietal epithelial cell activation induces collagen secretion and thickening of Bowman's capsule in diabetes

AU - Holderied, Alexander

AU - Romoli, Simone

AU - Eberhard, Jonathan

AU - Konrad, Lukas A

AU - Devarapu, Satish K

AU - Marschner, Julian A

AU - Müller, Susanna

AU - Anders, Hans-Joachim

PY - 2015/3

Y1 - 2015/3

N2 - The metabolic and hemodynamic alterations in diabetes activate podocytes to increase extracellular matrix (ECM) production, leading to thickening of the glomerular basement membrane (GBM). We hypothesized that diabetes would activate parietal epithelial cells (PECs) in a similar manner and cause thickening of Bowman's capsules. Periodic acid Schiff staining of human kidney biopsies of 30 patients with diabetic nephropathy (DN) revealed a significantly thicker Bowman's capsule as compared with 20 non-diabetic controls. The average thickness was 4.55±0.21 μm in the group of patients with DN compared with 2.92±0.21 μm in the group of non-diabetic controls (P<0.001). Transmission electron microscopy confirmed this finding. In vitro, short-term exposure of human PECs to hyperglycemic conditions (30 mM glucose) advanced glycation end products (100 μg/ml) or transforming growth factor-β1 (TGF-β1; 5 ng/ml) increased the mRNA expression of collagen type I α-1, collagen type IV (all six α-chains), bamacan, nidogen 1, laminin α-1, and perlecan. Western blot and colorimetric collagen assays confirmed these results for collagen type IV at the protein level. The production and secretion of TGF-β1 as a possible positive feedback loop was excluded as a mechanism for the autocrine activation of human PECs. To validate these findings in vivo, activation of the PECs was assessed by immunohistochemical staining for CD44 of 12 human biopsy cases with DN. Thickening of the Bowman's capsule showed strong association with CD44-positive PECs. In summary, metabolic alterations in diabetes activate PECs to increase the expression and secretion of Bowman's capsule proteins. This process may contribute to the thickening of the Bowman's capsule, similar to the thickening of the GBM that is driven by activated podocytes. These data may also imply that activated PECs contribute to ECM production once they migrate to the glomerular tuft, a process resulting in glomerular scaring, for example, in diabetic glomerulosclerosis.

AB - The metabolic and hemodynamic alterations in diabetes activate podocytes to increase extracellular matrix (ECM) production, leading to thickening of the glomerular basement membrane (GBM). We hypothesized that diabetes would activate parietal epithelial cells (PECs) in a similar manner and cause thickening of Bowman's capsules. Periodic acid Schiff staining of human kidney biopsies of 30 patients with diabetic nephropathy (DN) revealed a significantly thicker Bowman's capsule as compared with 20 non-diabetic controls. The average thickness was 4.55±0.21 μm in the group of patients with DN compared with 2.92±0.21 μm in the group of non-diabetic controls (P<0.001). Transmission electron microscopy confirmed this finding. In vitro, short-term exposure of human PECs to hyperglycemic conditions (30 mM glucose) advanced glycation end products (100 μg/ml) or transforming growth factor-β1 (TGF-β1; 5 ng/ml) increased the mRNA expression of collagen type I α-1, collagen type IV (all six α-chains), bamacan, nidogen 1, laminin α-1, and perlecan. Western blot and colorimetric collagen assays confirmed these results for collagen type IV at the protein level. The production and secretion of TGF-β1 as a possible positive feedback loop was excluded as a mechanism for the autocrine activation of human PECs. To validate these findings in vivo, activation of the PECs was assessed by immunohistochemical staining for CD44 of 12 human biopsy cases with DN. Thickening of the Bowman's capsule showed strong association with CD44-positive PECs. In summary, metabolic alterations in diabetes activate PECs to increase the expression and secretion of Bowman's capsule proteins. This process may contribute to the thickening of the Bowman's capsule, similar to the thickening of the GBM that is driven by activated podocytes. These data may also imply that activated PECs contribute to ECM production once they migrate to the glomerular tuft, a process resulting in glomerular scaring, for example, in diabetic glomerulosclerosis.

KW - Adult

KW - Antigens, CD44

KW - Blotting, Western

KW - Bowman Capsule

KW - Cells, Cultured

KW - Collagen

KW - Diabetic Nephropathies

KW - Epithelial Cells

KW - Female

KW - Gene Expression

KW - Glucose

KW - Glycosylation End Products, Advanced

KW - Humans

KW - Immunohistochemistry

KW - Kidney Glomerulus

KW - Male

KW - Microscopy, Electron, Transmission

KW - Reverse Transcriptase Polymerase Chain Reaction

KW - Transforming Growth Factor beta1

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1038/labinvest.2014.160

DO - 10.1038/labinvest.2014.160

M3 - SCORING: Journal article

C2 - 25531564

VL - 95

SP - 273

EP - 282

JO - LAB INVEST

JF - LAB INVEST

SN - 0023-6837

IS - 3

ER -