|
1
|
Takahashi K, Mulliken JB, Kozakewich HP,
Rogers RA, Folkman J and Ezekowitz RA: Cellular markers that
distinguish the phases of hemangioma during infancy and childhood.
J Clin Invest. 93:2357–2364. 1994.PubMed/NCBI View Article : Google Scholar
|
|
2
|
Yuan SM, Guo Y, Wang Q, Xu Y, Wang M, Chen
HN and Shen WM: Over-expression of PPAR-γ2 gene enhances the
adipogenic differentiation of hemangioma-derived mesenchymal stem
cells in vitro and in vivo. Oncotarget. 8:115817–115828.
2017.PubMed/NCBI View Article : Google Scholar
|
|
3
|
Ji Y, Chen S, Li K, Li L, Xu C and Xiang
B: Signaling pathways in the development of infantile hemangioma. J
Hematol Oncol. 7(13)2014.PubMed/NCBI View Article : Google Scholar
|
|
4
|
Mitra R, Fitzsimons HL, Hale T, Tan ST,
Gray C and White MPJ: Recent advances in understanding the
molecular basis of infantile haemangioma development. Br J
Dermatol. 191:661–669. 2024.PubMed/NCBI View Article : Google Scholar
|
|
5
|
Holm A, Mulliken JB and Bischoff J:
Infantile hemangioma: The common and enigmatic vascular tumor. J
Clin Invest. 134(e172836)2024.PubMed/NCBI View Article : Google Scholar
|
|
6
|
Chen Q, Zheng J and Bian Q: Cell fate
regulation during the development of infantile hemangioma. J Invest
Dermatol. 145:266–279. 2025.PubMed/NCBI View Article : Google Scholar
|
|
7
|
Chen ZT, Cui MJ, Guo SK, Wang ZL, Zhai QL,
Duan YF, Zhou T, Yang RM, Zheng JW, Liu BQ and Liu C: Single-cell
RNA sequencing reveals bidirectional development of infantile
hemangioma. J Invest Dermatol. 146:1344–1353. 2026.PubMed/NCBI View Article : Google Scholar
|
|
8
|
Yang L, Gong X, Xu Y, Zhang K, Xiang S,
Zhang Y and Ji Y: Immune microenvironment of infantile hemangioma:
Cellular dynamics, molecular networks, and emerging
immunomodulatory strategies. Front Immunol.
17(1908287)2026.PubMed/NCBI View Article : Google Scholar
|
|
9
|
Harris RP, Helfand M, Woolf SH, Lohr KN,
Mulrow CD, Teutsch SM and Atkins D: Methods Work Group, Third U.S.
Preventive Services Task Force. REPRINT oF: Current methods of the
U.S. preventive services task force: A review of the process. Am J
Prev Med. 58:316–331. 2020.PubMed/NCBI View Article : Google Scholar
|
|
10
|
Zhang X, Dai XY, Qian JY, Xu F, Wang ZW,
Xia T, Zhou XJ, Li XX, Shi L, Wei JF and Ding Q: SMC1A regulated by
KIAA1429 in m6A-independent manner promotes EMT progress in breast
cancer. Mol Ther Nucleic Acids. 27:133–146. 2021.PubMed/NCBI View Article : Google Scholar
|
|
11
|
Wang L, Zou Y, Huang Z, Wang W, Li J, Bi J
and Huo R: KIAA1429 promotes infantile hemangioma regression by
facilitating the stemness of hemangioma endothelial cells. Cancer
Sci. 114:1569–1581. 2023.PubMed/NCBI View Article : Google Scholar
|
|
12
|
Yu Y, Flint AF, Mulliken JB, Wu JK and
Bischoff J: Endothelial progenitor cells in infantile hemangioma.
Blood. 103:1373–1375. 2004.PubMed/NCBI View Article : Google Scholar
|
|
13
|
Li Y, Zhu X, Kong M, Chen S, Bao J and Ji
Y: Three-dimensional microtumor formation of infantile
hemangioma-derived endothelial cells for mechanistic exploration
and drug screening. Pharmaceuticals (Basel).
15(1393)2022.PubMed/NCBI View Article : Google Scholar
|
|
14
|
Serrano M, Hannon GJ and Beach D: A new
regulatory motif in cell-cycle control causing specific inhibition
of cyclin D/CDK4. Nature. 366:704–707. 1993.PubMed/NCBI View
Article : Google Scholar
|
|
15
|
Li J, Poi MJ and Tsai MD: Regulatory
mechanisms of tumor suppressor P16(INK4A) and their relevance to
cancer. Biochemistry. 50:5566–5582. 2011.PubMed/NCBI View Article : Google Scholar
|
|
16
|
Lorusso B, Nogara A, Fioretzaki R,
Corradini E, Bove R, Roti G, Gherli A, Montanaro A, Monica G,
Cavazzini F, et al: CD26 is differentially expressed throughout the
life cycle of infantile hemangiomas and characterizes the
proliferative phase. Int J Mol Sci. 25(9760)2024.PubMed/NCBI View Article : Google Scholar
|
|
17
|
Ritter MR, Moreno SK, Dorrell MI, Rubens
J, Ney J, Friedlander DF, Bergman J, Cunningham BB, Eichenfield L,
Reinisch J, et al: Identifying potential regulators of infantile
hemangioma progression through large-scale expression analysis: A
possible role for the immune system and indoleamine 2,3 dioxygenase
(IDO) during involution. Lymphat Res Biol. 1:291–299.
2003.PubMed/NCBI View Article : Google Scholar
|
|
18
|
Zhang W, Chen G, Wang FQ, Ren JG, Zhu JY,
Cai Y, Zhao JH, Jia J and Zhao YF: Macrophages contribute to the
progression of infantile hemangioma by regulating the proliferation
and differentiation of hemangioma stem cells. J Invest Dermatol.
135:3163–3172. 2015.PubMed/NCBI View Article : Google Scholar
|
|
19
|
Wang FQ, Chen G, Zhu JY, Zhang W, Ren JG,
Liu H, Sun ZJ, Jia J and Zhao YF: M2-polarised macrophages in
infantile haemangiomas: Correlation with promoted angiogenesis. J
Clin Pathol. 66:1058–1064. 2013.PubMed/NCBI View Article : Google Scholar
|
|
20
|
Zhu Z, Jiang X, Wang F, Zhao L and Song Q:
Decoding infantile hemangioma: Cellular dynamics, molecular
signals, and microenvironmental influences. Front Oncol.
15(1675194)2025.PubMed/NCBI View Article : Google Scholar
|
|
21
|
Wu KQ, Muratore CS, So EY, Sun C,
Dubielecka PM, Reginato AM and Liang OD: M1 macrophage-induced
endothelial-to-mesenchymal transition promotes infantile hemangioma
regression. Am J Pathol. 187:2102–2111. 2017.PubMed/NCBI View Article : Google Scholar
|
|
22
|
Medici D, Shore EM, Lounev VY, Kaplan FS,
Kalluri R and Olsen BR: Conversion of vascular endothelial cells
into multipotent stem-like cells. Nat Med. 16:1400–1406.
2010.PubMed/NCBI View
Article : Google Scholar
|
|
23
|
Greenberger S, Yuan S, Walsh LA, Boscolo
E, Kang KT, Matthews B, Mulliken JB and Bischoff J: Rapamycin
suppresses self-renewal and vasculogenic potential of stem cells
isolated from infantile hemangioma. J Invest Dermatol.
131:2467–2476. 2011.PubMed/NCBI View Article : Google Scholar
|
|
24
|
Liu L, Lin S, Bai J and Zhang B:
Integrative bioinformatics analysis of pyroptosis-related genes and
analysis of immune cell infiltration in infantile hemangioma
regression. Clin Cosmet Investig Dermatol. 18:291–302.
2025.PubMed/NCBI View Article : Google Scholar
|
|
25
|
Liu J, Zhong W, Wang R, Wang P, Tong G,
Chai M, Sun Y, Zhu T, Huang C, Yang S, et al: Macrophage
ferroptotic resistance is required for the progression of infantile
hemangioma. J Am Heart Assoc. 14(e034261)2025.PubMed/NCBI View Article : Google Scholar
|
|
26
|
Tan ST, Velickovic M, Ruger BM and Davis
PF: Cellular and extracellular markers of hemangioma. Plast
Reconstr Surg. 106:529–538. 2000.PubMed/NCBI View Article : Google Scholar
|
|
27
|
Wu M, Chen Y, Feng L, Dai H, Fang S and Xu
J: MiR-206 promotes extracellular matrix accumulation and relieves
infantile hemangioma through targeted inhibition of DNMT3A. Cell
Cycle. 20:978–992. 2021.PubMed/NCBI View Article : Google Scholar
|
|
28
|
Zhao ZL, Liu C, Wang QZ, Wu HW and Zheng
JW: Engineered exosomes for targeted delivery of miR-187-3p
suppress the viability of hemangioma stem cells by targeting Notch
signaling. Ann Transl Med. 10(621)2022.PubMed/NCBI View Article : Google Scholar
|
|
29
|
Li Z, Cao Z, Li N, Wang L, Fu C, Huo R, Xu
G, Tian C and Bi J: M2 macrophage-derived exosomal lncRNA
MIR4435-2HG promotes progression of infantile hemangiomas by
targeting HNRNPA1. Int J Nanomedicine. 18:5943–5960.
2023.PubMed/NCBI View Article : Google Scholar
|
|
30
|
Johnson A, Zhang H, Gonzalez SR, Lee M,
Wei T and Richter G: Presence of estrogen and progesterone
receptors in proliferating and involuting infantile hemangiomas. J
Plast Reconstr Aesthet Surg. 74:3061–3065. 2021.PubMed/NCBI View Article : Google Scholar
|
|
31
|
Munabi NCO, Tan QK, Garzon MC, Behr GG,
Shawber CJ and Wu JK: Growth hormone induces recurrence of
infantile hemangiomas after apparent involution: Evidence of growth
hormone receptors in infantile hemangioma. Pediatr Dermatol.
32:539–543. 2015.PubMed/NCBI View Article : Google Scholar
|
|
32
|
Hou F, Dai Y, Fan CY, Suen JY and Richter
GT: Estrogen is involved in hemangioma regression associated with
mast cells. Orphanet J Rare Dis. 13(181)2018.PubMed/NCBI View Article : Google Scholar
|
|
33
|
Maclellan RA, Konczyk DJ, Goss JA and
Greene AK: Analysis of follicle-stimulating hormone receptor in
infantile hemangioma. Ann Plast Surg. 80 (4 Suppl 4):S211–S213.
2018.PubMed/NCBI View Article : Google Scholar
|
|
34
|
Hong Z, Kuang J, Guo Y, Zhou G, Zhu Z and
Jiang L: Effects of follicle-stimulating hormone on the
proliferation and apoptosis of infantile hemangioma stem cells.
Biochem Biophys Rep. 35(101551)2023.PubMed/NCBI View Article : Google Scholar
|
|
35
|
Khan ZA, Boscolo E, Picard A, Psutka S,
Melero-Martin JM, Bartch TC, Mulliken JB and Bischoff J:
Multipotential stem cells recapitulate human infantile hemangioma
in immunodeficient mice. J Clin Invest. 118:2592–2599.
2008.PubMed/NCBI View Article : Google Scholar
|
|
36
|
Arasiewicz H and Dec M: Targeted therapies
in infantile hemangiomas and vascular malformations: From
β-blockers to PI3K/AKT/mTOR inhibitors. J Cell Mol Med.
30(e71103)2026.PubMed/NCBI View Article : Google Scholar
|
|
37
|
Yang K, Qiu T, Zhou J, Gong X, Zhang X,
Lan Y, Zhang Z and Ji Y: Blockage of glycolysis by targeting PFKFB3
suppresses the development of infantile hemangioma. J Transl Med.
21(85)2023.PubMed/NCBI View Article : Google Scholar
|
|
38
|
Wang F, Li H, Lou Y, Xie J, Cao D and
Huang X: Insulin-like growth factor I promotes adipogenesis in
hemangioma stem cells from infantile hemangiomas. Mol Med Rep.
19:2825–2830. 2019.PubMed/NCBI View Article : Google Scholar
|
|
39
|
Ritter MR, Dorrell MI, Edmonds J,
Friedlander SF and Friedlander M: Insulin-like growth factor 2 and
potential regulators of hemangioma growth and involution identified
by large-scale expression analysis. Proc Natl Acad Sci USA.
99:7455–7460. 2002.PubMed/NCBI View Article : Google Scholar
|
|
40
|
Zhang K, Wang F, Huang J, Lou Y, Xie J, Li
H, Cao D and Huang X: Insulin-like growth factor 2 promotes the
adipogenesis of hemangioma-derived stem cells. Exp Ther Med.
17:1663–1669. 2019.PubMed/NCBI View Article : Google Scholar
|
|
41
|
Harbi S, Wang R, Gregory M, Hanson N,
Kobylarz K, Ryan K, Deng Y, Lopez P, Chiriboga L and Mignatti P:
Infantile hemangioma originates from a dysregulated but not fully
transformed multipotent stem cell. Sci Rep. 6(35811)2016.PubMed/NCBI View Article : Google Scholar
|
|
42
|
Madsen MS, Siersbæk R, Boergesen M,
Nielsen R and Mandrup S: Peroxisome proliferator-activated receptor
γ and C/EBPα synergistically activate key metabolic adipocyte genes
by assisted loading. Mol Cell Biol. 34:939–954. 2014.PubMed/NCBI View Article : Google Scholar
|
|
43
|
Choi SK, Park S, Jang S, Cho HH, Lee S,
You S, Kim SH and Moon HS: Cascade regulation of PPARγ(2) and
C/EBPα signaling pathways by celastrol impairs adipocyte
differentiation and stimulates lipolysis in 3T3-L1 adipocytes.
Metabolism. 65:646–654. 2016.PubMed/NCBI View Article : Google Scholar
|
|
44
|
Maimaiti A, Aierken Y, Zhou L, He J,
Abudureyimu A and Li SX: Inhibiting interleukin-6/signal
transducers and activators of transduction-3/hypoxia-inducible
factor-1α signaling pathway suppressed the growth of infantile
hemangioma. Eur J Pediatr Surg. 33:158–166. 2023.PubMed/NCBI View Article : Google Scholar
|
|
45
|
Sun ZJ, Cai Y, Chen G, Wang R, Jia J, Chen
XM, Zheng LW and Zhao YF: LMO2 promotes angiogenesis probably by
up-regulation of bFGF in endothelial cells: An implication of its
pathophysiological role in infantile haemangioma. Histopathology.
57:622–632. 2010.PubMed/NCBI View Article : Google Scholar
|
|
46
|
Wu JK, Adepoju O, De Silva D, Baribault K,
Boscolo E, Bischoff J and Kitajewski J: A switch in Notch gene
expression parallels stem cell to endothelial transition in
infantile hemangioma. Angiogenesis. 13:15–23. 2010.PubMed/NCBI View Article : Google Scholar
|
|
47
|
Wang W, Chen S, Wang Y, Jie C and Shen W:
Effects of Notch signaling on proliferation, angiogenesis, and
adipogenesis of hemangioma-derived stem cells. Eur J Histochem.
69(4241)2025.PubMed/NCBI View Article : Google Scholar
|
|
48
|
Zhang H, Wei T, Johnson A, Sun R, Richter
G and Strub GM: NOTCH pathway activation in infantile hemangiomas.
J Vasc Surg Venous Lymphat Disord. 9:489–496. 2021.PubMed/NCBI View Article : Google Scholar
|
|
49
|
Kowalska M, Dębek W and Matuszczak E:
Infantile hemangiomas: An update on pathogenesis and treatment. J
Clin Med. 10(4631)2021.PubMed/NCBI View Article : Google Scholar
|
|
50
|
Chen S, Zhuang K, Sun K, Yang Q, Ran X, Xu
X, Mu C, Zheng B, Lu Y, Zeng J, et al: Itraconazole induces
regression of infantile hemangioma via downregulation of the
platelet-derived growth factor-D/PI3K/Akt/mTOR pathway. J Invest
Dermatol. 139:1574–1582. 2019.PubMed/NCBI View Article : Google Scholar
|
|
51
|
Munabi NCO, England RW, Edwards AK,
Kitajewski AA, Tan QK, Weinstein A, Kung JE, Wilcox M, Kitajewski
JK, Shawber CJ and Wu JK: Propranolol targets hemangioma stem cells
via cAMP and mitogen-activated protein kinase regulation. Stem
Cells Transl Med. 5:45–55. 2016.PubMed/NCBI View Article : Google Scholar
|
|
52
|
Pan WK, Li P, Guo ZT, Huang Q and Gao Y:
Propranolol induces regression of hemangioma cells via the
down-regulation of the PI3K/Akt/eNOS/VEGF pathway. Pediatr Blood
Cancer. 62:1414–1420. 2015.PubMed/NCBI View Article : Google Scholar
|
|
53
|
Cai B, Lin Q, Ke R, Chen L, Wan X, Ni X,
Shan X and Wang B: Determinants of proliferation and involution in
infantile hemangioma: Macrophage crosstalk, endothelial plasticity,
and metabolic rewiring. Front Pediatr. 14(1847957)2026.PubMed/NCBI View Article : Google Scholar
|
|
54
|
Zaaroura H, Tibi A, Avitan-Hersh E and
Khamaysi Z: Our experience in treating infantile hemangioma:
Prognostic factors for relapse after propranolol discontinuation.
Adv Ther. 42:537–547. 2025.PubMed/NCBI View Article : Google Scholar
|
|
55
|
Li Q, Xiao L, Su M, Chen H, Zhang H, Cao
N, Jiang L, Liu X and Zhang G: Factors influencing treatment
duration of oral propranolol in infantile hemangioma: A five-year
retrospective analysis. Front Pediatr. 13(1693660)2026.PubMed/NCBI View Article : Google Scholar
|
|
56
|
Li M, Wang X, Yang E, Li Y, Geng Y, Chen
Z, Huang S, Zhang D and Wu H: OTUB1 catalytic-independently
deubiquitinates TGFBI and mediates the angiogenesis in infantile
hemangioma by regulating glycolysis. Arterioscler Thromb Vasc Biol.
43:654–673. 2023.PubMed/NCBI View Article : Google Scholar
|
|
57
|
Chen Q, Rong H, Zhang L, Wang Y, Bian Q
and Zheng J: KLF2 orchestrates pathological progression of
infantile hemangioma through hemangioma stem cell fate decisions. J
Invest Dermatol. 144:1850–1864.e9. 2024.PubMed/NCBI View Article : Google Scholar
|
|
58
|
Kong M, Li Y, Wang K, Zhang S and Ji Y:
Infantile hemangioma models: Is the needle in a haystack? J Transl
Med. 21(308)2023.PubMed/NCBI View Article : Google Scholar
|
|
59
|
Holm A, Graus MS, Wylie-Sears J, Tan JWH,
Alvarez-Harmon M, Borgelt L, Nasim S, Chung L, Jain A, Sun M, et
al: An endothelial SOX18-mevalonate pathway axis enables
repurposing of statins for infantile hemangioma. J Clin Invest.
135(e179782)2025.PubMed/NCBI View Article : Google Scholar
|
|
60
|
Yang E, Wang X, Huang S, Li M, Li Y, Geng
Y, Liu X, Chen Z, Zhang D and Wu H: Shikonin reverses pyruvate
kinase isoform M2-mediated propranolol resistance in infantile
hemangioma through reactive oxygen species-induced autophagic
dysfunction. Cancer Sci. 114:806–821. 2023.PubMed/NCBI View Article : Google Scholar
|
|
61
|
Shah SD, Baselga E, McCuaig C, Pope E,
Coulie J, Boon LM, Garzon MC, Haggstrom AN, Adams D, Drolet BA, et
al: Rebound growth of infantile hemangiomas after propranolol
therapy. Pediatrics. 137(e20151754)2016.PubMed/NCBI View Article : Google Scholar
|
|
62
|
Mitra R, Hale TK, Fitzsimons HL, Gray C
and White MPJ: A novel three-dimensional model of infantile
haemangioma. Br J Dermatol. 192:874–882. 2025.PubMed/NCBI View Article : Google Scholar
|
