Table 1. Agents, molecules, and genes associated with podocyte injury and foot process effacement.
| Means of injury | Category | Agent/Molecule/Gene | References |
|---|---|---|---|
| Toxicity | Actin reorganization | Adriamycin | 40– 49 |
| Diphtheria toxin | 50– 52 | ||
| Indoxyl sulfate | 53 | ||
| Puromycin aminonucleoside | 6, 24– 39 | ||
| Shigatoxin | 54– 56 | ||
| Immunologic | Actin reorganization | Complement proteins | 66– 70 |
| Lipopolysaccharides | 57– 63 | ||
| Polyinosinic-polycytidylic acid | 65 | ||
| Anti-GBM antibodies | Rabbit anti-mouse GBM antiserum | 71– 74 | |
| Rabbit anti-rat GBM antiserum | 75, 76 | ||
| Sheep anti-rabbit GBM antiserum | 77, 78 | ||
| Charge distortion | Podocyte polarity | Poly-L-lysine | 85 |
| Protamine sulfate | 30, 79– 87 | ||
| Sialidase | 11, 88 | ||
| Signaling pathway
activation |
Actin reorganization
and motility |
Angiopoietin-like3 (ANGPTL3) | 271 |
| B7-1 (CD80) | 57, 272 | ||
| Cytosolic cathepsin L (cCATL) | 61– 64 | ||
| Glucose | 273– 277 | ||
| Glutamine | 64 | ||
| Insulin | 227 | ||
| Integrin β3 (ITGB3) | 60, 278 | ||
| Tumor necrosis factor-α (TNF-α) | 279– 281 | ||
| Transient receptor potential cation channel 5/6 (TRPC5 and TRPC6) | 282 | ||
| Urokinase-type plasminogen activator receptor (uPAR) | 60 | ||
| Apoptosis and
mitochondrial dysfunction |
Albumin | 283– 285 | |
| Aldosterone | 286– 288 | ||
| Angiopoietin-like 3 (ANGPTL3) | 289 | ||
| Angiotensin II | 290– 294 | ||
| Fatty acids | 295– 297 | ||
| Glucose | 232, 294, 298 | ||
| IGF-binding protein-3 (IGFBP-3) | 299 | ||
| Oxidized low-density lipoprotein (LDL) | 300 | ||
| Transforming growth factor-β1 (TGF-β1) | 237, 301– 304 | ||
| Autophagy | Angiotensin II | 305 | |
| Glucose | 306 | ||
| EMT | Endothelin-1 (ET-1) | 263 | |
| Integrin-linked kinase (ILK) | 212 | ||
| Puromycin aminonucleoside | 262 | ||
| Transforming growth factor-β1 (TGF-β1) | 308 | ||
| Proliferative | Negative factor (NEF) | 309, 310 | |
| Tumor necrosis factor-α (TNF-α) | 311 | ||
| Proteinuric | Hypo-sialylated angiopoietin-like 4 (ANGPTL4) | 32 | |
| Soluble urokinase-type plasminogen activator receptor (suPAR) | 278 | ||
| Anti-proteinuric | Circulating sialylated angiopoietin-like 4 (ANGPTL4) | 312 | |
| Survival | Activated protein C (APC) | 313, 314 | |
| Bone morphogenetic protein-7 (BMP7) | 277, 299, 315 | ||
| Insulin-like growth factor-II (IGF-II) | 228 | ||
| Vascular endothelial growth factor A (VEGF-A) | 316– 318 | ||
| Vascular endothelial growth factor C (VEGF-C) | 318, 319 | ||
| Genetic modification | Actin-regulating
proteins and enzymes |
aarF domain containing kinase 4 ( ADCK4) | 99 |
| α-actinin 4 ( ACTN4) | 93– 96 | ||
| Anillin ( ANLN) | 100 | ||
| Apolipoprotein L1 ( APOL1) | 101 | ||
| RhoA-activated Rac1 GTPase-activating protein 24 ( ARHGAP24) | 102 | ||
| Rho guanine nucleotide dissociation inhibitor-α ( ARHGDIA) | 103– 105 | ||
| Claudin-1 ( CLDN1) | 106 | ||
| Chloride intracellular channel 5A ( CLIC5A) | 107 | ||
| Cofilin-1 ( CFL1) | 108, 109 | ||
| Dynamin ( DYN) | 61, 97, 98 | ||
| Ezrin ( EZR) | 110 | ||
| Inverted formin 2 ( INF2) | 111– 114 | ||
| Kidney ankyrin repeat-containing protein (
KANK1,
KANK2, and
KANK4) |
115 | ||
| Neuronal Wiskott-Aldrich syndrome protein ( N-WASP) | 116 | ||
| Class II phosphoinositide 3-kinase C2 α ( PI3KC2α) | 117 | ||
| Phospholipase C ε1 ( PLCE1) | 118 | ||
| Rac1 ( RAC1) | 119, 120 | ||
| Rhophilin 1 ( RHPN1) | 121 | ||
| Schwannomin interacting protein 1 ( SCHIP1) | 122 | ||
| Synaptopodin ( SYNPO) | 90– 92 | ||
| WT1-interacting protein ( WTIP) | 123 | ||
| Lysosomal protein | Lysosome membrane protein 2 ( SCARB2/LIMP2) | 190 | |
| Mitochondrial
proteins |
Coenzyme Q 2 ( COQ2) | 191 | |
| Coenzyme Q 6 ( COQ6) | 192 | ||
| Mpv17 ( MPV17) | 193 | ||
| Mitochondrial tRNA leucine 1 ( MTTL1) | 194 | ||
| Prohibitin ring complex subunit prohibitin-2 ( PHB2) | 195 | ||
| Transcription factors | C-Maf-inducing protein ( CMIP) | 242, 243 | |
| Forkhead box C2 ( FOXC2) | 244 | ||
| Hypoxia-inducible factor 1 α ( HIF1A) | 245– 247 | ||
| Krüppel-like factor 6 ( KLF6) | 248 | ||
| LIM homeobox transcription factor 1 β ( LMX1B) | 249– 254 | ||
| V-Maf avian musculoaponeurotic fibrosarcoma oncogene homolog
B ( MAFB) |
255, 256 | ||
| Nuclear factor of activated T cells ( NFAT) | 257, 258 | ||
| Paired box gene 2 ( PAX2) | 259 | ||
| Podocyte-expressed 1/Transcription factor 21 ( POD1/TCF21) | 260 | ||
| Peroxisome proliferator-activated receptor-α (PPARA) | 261 | ||
| Snail family zinc finger 1 ( SNAI1) | 262, 263 | ||
| Wilm’s tumor 1 ( WT-1) | 264– 268 | ||
| Zinc finger E-box-binding homeobox 2 ( ZEB2) | 269 | ||
| Zinc fingers and homeoboxes 1/2/3 ( ZHX1, ZHX2, ZHX3) | 270 | ||
| Apoptosis and
survival |
Dendrin ( DDN) | 203 | |
| Survivin ( BIRC5) | 204 | ||
| Vascular endothelial growth factor A ( VEGF-A) | 207, 208 | ||
| Yes-associated protein ( YAP) | 205, 206 | ||
| Autophagy regulating
proteins |
Autophagy-related 5 ( ATG5) | 196 | |
| Mammalian target of rapamycin ( MTOR) | 197 | ||
| Prorenin receptor ( PRR) | 198– 200 | ||
| Class III phosphoinositide 3-kinase/Vacuolar protein sorting 34
( PIK3C3/VPS34) |
201, 202 | ||
| Signaling pathway
activation |
β-catenin ( CTNNB1) | 209 | |
| Notch intracellular domain 1 ( ICN1) | 210 | ||
| Integrin-linked kinase ( ILK) | 211– 213 | ||
| Negative factor ( NEF) | 214, 215 | ||
| Notch’s intracellular domain ( NOTCH-IC) | 216 | ||
| Septin ( SEPT7) | 217 | ||
| Transforming growth factor β ( TGF-β) | 218 | ||
| Tuberous sclerosis complex 1 ( TSC1) | 219 | ||
| Vpr-binding protein ( VPR) | 215 | ||
| Wingless-type MMTV integration site family 1 ( WNT1) | 220 | ||
| Signaling pathway
reduction |
Akt2 ( AKT2) | 221 | |
| PINCH-1–binding ankyrin repeat domain of ILK ( ANK) | 222 | ||
| Angiotensin II receptor 2 ( AT2) | 223 | ||
| β-catenin ( CTNNB1) | 209, 224, 225 | ||
| Diaphanous interacting protein ( DIP) | 226 | ||
| Dickkopf WNT signaling pathway inhibitor 1 ( DKK1) | 209, 220, 225 | ||
| Insulin-like growth factor-I receptor ( IGF-IR) | 195, 227– 229 | ||
| Insulin receptor ( INSR) | 195, 227, 229 | ||
| NF-κB essential modulator ( NEMO) | 230, 231 | ||
| Notch-1 ( NOTCH1) | 232 | ||
| Notch-3 ( NOTCH3) | 233 | ||
| 3-phosphoinositide-dependent kinase-1 ( PDK1) | 234 | ||
| Rapamycin-sensitive adaptor protein of mTOR ( RAPTOR) | 219, 235 | ||
| Recombining binding protein suppressor of hairless ( RBPSUH) | 216 | ||
| Rapamycin-insensitive subunit of mTOR ( RICTOR) | 221, 235 | ||
| SH2-domain-containing inositol polyphosphate 5-phosphatase 2
( SHIP2) |
236 | ||
| SMAD family member 2/3 ( SMAD2, SMAD3) | 237 | ||
| Signal transducer and activator of transcription 3 ( STAT3) | 238– 240 | ||
| Slit diaphragm-
associated proteins |
CD2-associated protein ( CD2AP) | 63, 92, 130, 131 | |
| Cysteine-rich motor neuron 1 ( CRIM1) | 142 | ||
| FAT atypical cadherin 1 ( FAT1) | 143 | ||
| Fyn proto-oncogene ( FYN) | 92, 144, 145 | ||
| IQ domain GTPase-activating protein 1 ( IQGAP1) | 146, 147 | ||
| MAGUK inverted 2 ( MAGI-2) | 148 | ||
| Myosin 1c ( MYO1C) | 149 | ||
| Myosin 1e ( MYO1E) | 150– 153 | ||
| Nck adaptor protein 1/2 ( NCK1, NCK2) | 86, 132, 133 | ||
| Nephrin ( NPHS1) | 124– 126 | ||
| Kin of IRRE-like 1 ( NEPH1) | 126, 154 | ||
| Podocin ( NPHS2) | 127– 129 | ||
| Transient receptor potential cation channel 6 ( TRPC6) | 134– 141 | ||
| Zonula occludens 1 ( ZO-1) | 155 | ||
| Podocyte polarity | A typical protein kinase Clambda/iota ( aPKCλ/ι) | 161– 163 | |
| Cdc42 ( CDC42) | 119, 160 | ||
| Glucosamine uridine diphospho–
N-acetylglucosamine 2-epimerase/
N-acetylmannosamine kinase ( GNE) |
89 | ||
| Podocalyxin ( PC) | 156, 157 | ||
| Protein‐tyrosine phosphatase receptor o/Glomerular epithelial protein 1
( PTPRO/GLEPP1) |
158, 159 | ||
| Van Gogh-like (planar cell polarity) protein 2 ( VANGL2) | 164– 166 | ||
| GBM-associated
proteins and enzymes |
CD9 ( CD9) | 171 | |
| CD151 ( CD151) | 172– 175 | ||
| Type IV collagen α3/α4/α5 ( COL4A3, COL4A4, and COL4A5) | 176– 178 | ||
| Discoidin domain receptor 1 ( DDR1) | 179 | ||
| Glypican 5 ( GPC5) | 180 | ||
| Integrin-linked kinase ( ILK) | 168, 181, 182 | ||
| Integrin α3 ( ITGA3) | 27, 167 | ||
| Integrin β1 ( ITGB1) | 168, 169 | ||
| Integrin β4 ( ITGB4) | 170 | ||
| Laminin β2 ( LAMB2) | 183– 186 | ||
| N-deacetylase/N-sulfotransferase ( NDST1) | 187 | ||
| RAP1 GTPase-activating protein ( RAP1GAP) | 188 | ||
| Talin 1 ( TLN1) | 189 |
GBM, glomerular basement membrane.