Table 1 Autophagy involved vessel calcification through inhibition and promotion cellular pathways
From: Multiple functions of autophagy in vascular calcification
Functions | Targeted genes | Animal models and cell culture | Involved genes |
|---|---|---|---|
VSMC osteogenic differentiation | |||
Autophagic inhibition | ANCR [34] | Animal model High calcitriol-induced mice model /male C57BL/6 Cell culture Mouse VSMCs of passages 3–8 | Atg5, BMP-2, Cbfa1/Runx2, LC3-I/II |
ERα [28] | Animal model 6-week-old female C57/BL6 mice were ovariectomized under anaesthesia (by Nembutal 40 mg/kg i.m.). Cell culture Mouse vascular smooth muscle cells (mVSMCs) were acquired from 8-week-old female C57/BL6 OVX mice or mice with intact ovaries. Patient tissue Renal arterial samples from a total of 10 pairs of uremic patients scheduled to undergo kidney transplantation and from healthy donors | Atg5, ALP, Cbfa1/Runx2, ERα, LC3-I/II | |
β-catenin [29] | Cell culture VSMCs from Male Sprague–Dawley (SD) rats aorta | Atg5, ALP, BMP-2, Beclin-1, Collagen I, Histone H2B, LC3, Osteocalcin, β-catenin | |
HIF-1a, PDK4, p62/SQSTM1 [30] | Cell culture VSMCs from Male SD rats aorta | Cbfa1/Runx2, HIF-1a, LC3, PDK4, p62/SQSTM1 | |
BECN1 [43] | Cell culture VSMCs from the descending thoracic aorta of rats, 293 T cells | Atg4b, Atg5, Atg7, Atg12, Atg16, BECN1, LC3B, LC3I/II, ULK1, VPS34 | |
mTOR, SOX9 [31] | Animal model 5‐weeks‐old chronic kidney disease rats (5/6 nephrectomy) Cell Culture VSMC lines | Beclin-1, Cbfa1/Runx2, LC3, LC3-II, miR-30b, mTOR, p‐mTOR, SOX9, S6K1, p‐S6K1 | |
GHSR/ERK [32] | Cell culture Mouse VSMCs | ALP, Cbfa1/Runx2, ERK, p-ERK, GHSR, JNK, p-JNK, p-p38, p38 | |
AMPK [44] | Animal model 3-month-old male SD rats Cell culture Primary VSMCs from thoracic aortas of male SD rats | AKT, p-AKT, Beclin-1, LC3, mTOR, p-mTOR | |
Autophagic promotion | ERK [47] | Animal model 6-week-old ApoE−/− mice (C57BL/6 J genetic background) Cell culture Human VSMCs (HA-VSMC, CRL-1999, ATCC, Manassas, VA, USA) | ALP, Beclin-1, DUSP5, ERK1/2, p-ERK1/2, LC3, LC3-I/II, mTOR, p-mTOR, p62/SQSTM1 |
Autophagic/ mitophagic apoptosis | |||
Autophagic inhibition | AMPK/mTOR/ULK1 [54] | Cell culture VSMCs from the aortas of 4-week-old SD rats | ALP, AMPK, p-AMPK, BMP-2, Cbfa1/Runx2, Caspase 3, Cleaved caspase 3, LC3-II, LC3-I, MGP, p62/SQSTM1, α-SMA, mTOR, ULK1, p-ULK1 |
Wnt/β-catenin [55] | Cell culture Primary HASMCs (human aortic smooth muscle cells) | BMP-2, Beclin-1, Bax, Bak, Bcl-2, Cbfa1/Runx2, β-catenin, Caspase 9, Caspase 3, LC3-II, p-mTOR, OPN, OPG, p62/SQSTM1, α-SMA | |
GAS6/AXL synthesis [56] | Cell culture Rat VSMCs | Axl, GAS6, LC3-II | |
Autophagic promotion | Drp1, BNIP3, NR4A1/DNA-PKcs/p53 [59] | Animal model 6-week-old male Wistar rats Cell culture Primary VSMCs from 6-week-old SD rat thoracic aortas | Bax, Bcl-2, BNIP3, BMP-2, Caspase 3, Cbfa1/Runx2, Drp1, DNA-PKcs, LC3, Mff, NR4A1, OPA1, p62/SQSTM1, p53, α-SMA, TOMM20, TOMM40, VDAC1 |
Osteogenesis | |||
Inhibition on osteoblast/osteoclast | AMPK mTOR [73] | Cell culture Primary human chondrocytes | ALP, Adiponectin, AMPK, p-AMPK (Thr172), Beclin-1, Caspase 3, Caspase 9, LC3-I, LC3-II, mTOR, p- mTOR, PARP |
EphrinB2, RhoA [74] | Animal model Dmp1Cre mice (Tg(Dmp1Cre)1Jqfe), EphrinB2-floxed (Efnb2tm1And) mice Cell culture Ocy454 cells and Kusa 4b10 cells | BNIP3, Eps8l1, Efnb2, Fam134b, Fbxo32, Klf1, Lama2, LC3-I, LC3-II, Pthlh, Peg3, RhoA, Trim63, Tspo2, Unc5a | |
Promotion on osteoblast/osteoclast | FGFR4, JNK, VPS34, beclin-1 [85] | Animal model Atg7fl/fl, GFP–LC3 mouse, Prx1-Cre, Col2a1-Cre, Fgf18- and Fgfr3-knockout mice, Fgfr4-knockout mice Cell culture GFP–LC3 primary chondrocytes, Fgf18+/− chondrocytes | Atg7, AKT, p-AKT, AMPKa, p-AMPKa, Beclin-1, p-BCL2, Collagen II, ERK1/2, p-ERK, FGFR3, FGFR4, GOLPH3, HA, Histone H3, JNK, p-JNK, p–c-JUN, LC3B, mTORC1, p-mTORC1, PDI, p38, p-p38, p62/SQSTM1, P70S6K, p-P70S6K, VPS34, 4EBP1, p-4EBP1 |
Regerentation (MSC-pericyte-VSMC-continuum) | |||
Autophagic inhibition | AKT, mTORC1, mTORC2 [89] | Animal model Male 10-week-old C57BL/6JRccHsd mice Cell culture Human bone marrow aspirates MSC | AKT, Bcl-2, Cleaved caspase 3, Calponin, Cbfa1/Runx2, Collagen IIA1, Collagen III, ERK1/2, ERK1/2Thr202/Tyr204, LC3B, MLCK, mTOR, Osteopontin, Osterix, p16INK4a, p62/SQSTM1, pp70S6KThr389, pp70S6KThr421/Ser424, pAKTSer473, pAKTThr308, p70-S6, Rictor, Raptor, SMA, SM22α |
AMPK [90] | Animal model 6-weeks-old male SD rats Cell culture Tenocytes isolated from 3-week-old SD rats achilles tendons | Cleaved caspase 3, Cleaved caspase 9, LC3A/B, p62/SQSTM1, p53, p21 | |
Cellular derived MV (Macrophage inflammatory) | |||
Autophagic inhibition | NOX-1, MAPK, MEK1, ERK1/2 [96] | Cell culture Primary rat VSMC from the descending thoracic aorta of CKD-MBD, Cy/ + rat | AT1R, Annexin II, Annexin V, Annexin VI, BMP-2, Cbfa1/Runx2, CD9, CD63, CD81, p-ERK1/2, Fetuin-A, p-MEK1, Myocardin, NOX-1, NOX-4, Osteocalcin, SM22α, SOD-1, SOD-2 |