Retinoic acid regulates endometriotic stromal cell growth through upregulation of Beclin1

article OA: closed CC0 ⤵ 9 in-corpus citations
AI-generated summary by claude@2026-06+body, 2026-06-11

Retinoic acid treatment enhanced autophagy in endometriotic stromal cells, and Beclin1 expression negatively correlated with endometriosis stage, with Beclin1 knockdown enhancing cell growth that RA treatment reversed.

One-sentence paraphrase of the abstract; not a substitute for reading it. No clinical advice. How this works

AI-generated deep summary by claude@2026-06, 2026-06-11 · read from full text

The study investigated how retinoic acid (RA) affects autophagy and endometriotic stromal cell (ESC) growth, focusing on Beclin1 as a potential mediator. Using Ishikawa cells and clinical ESCs, the authors measured autophagy marker mRNA/protein levels after RA treatment, analyzed Beclin1 expression in endometriosis clinical samples, and tested how Beclin1 knockdown and autophagy inhibition (chloroquine) altered ESC sensitivity to RA. RA increased autophagy in ESCs, Beclin1 expression correlated negatively with endometriosis stage, and Beclin1 knockdown enhanced ESC growth, an effect reversed by RA. Beclin1 knockdown and chloroquine did not increase ESC sensitivity to RA, and the paper explicitly notes no human participant or animal studies were performed by the authors. This paper is centrally about endometriosis — it examines RA-induced autophagy and Beclin1 regulation in endometriotic stromal cells.

Read from the paper's body, not the abstract. Not a substitute for reading the paper. No clinical advice. How this works

Abstract

PurposeTo elucidate the role of retinoic acid (RA) in autophagy-mediated endometriosis.MethodsThe mRNA and protein expressions of autophagy markers were examined in Ishikawa cells and endometriotic stromal cells (ESCs) after RA treatment. Beclin1 expression was specifically analyzed in clinical samples of endometriosis. The effect of Beclin1 knockdown on ESC growth was assessed, and the effect of autophagy inhibition on the sensitivity of endometriotic cells to RA was analyzed.ResultsRA treatment enhanced the autophagy in ESCs, and Beclin1 expression showed a negative correlation with the clinical stage of endometriosis. Beclin1 knockdown enhanced ESC growth, whereas RA treatment reversed this effect. Furthermore, inhibition of autophagy by chloroquine (CQ) and Beclin1 knockdown did not show any positive effect on the sensitivity of endometriotic cells to RA.ConclusionsRA treatment induces autophagy and Beclin1 may play an important role in endometriosis progression.
Full text 8,193 characters · extracted from oa-doi-fallback · 5 sections · click to expand

Abstract

Purpose To elucidate the role of retinoic acid (RA) in autophagy-mediated endometriosis.

Methods

The mRNA and protein expressions of autophagy markers were examined in Ishikawa cells and endometriotic stromal cells (ESCs) after RA treatment. Beclin1 expression was specifically analyzed in clinical samples of endometriosis. The effect of Beclin1 knockdown on ESC growth was assessed, and the effect of autophagy inhibition on the sensitivity of endometriotic cells to RA was analyzed.

Results

RA treatment enhanced the autophagy in ESCs, and Beclin1 expression showed a negative correlation with the clinical stage of endometriosis. Beclin1 knockdown enhanced ESC growth, whereas RA treatment reversed this effect. Furthermore, inhibition of autophagy by chloroquine (CQ) and Beclin1 knockdown did not show any positive effect on the sensitivity of endometriotic cells to RA.

Conclusions

RA treatment induces autophagy and Beclin1 may play an important role in endometriosis progression. Similar content being viewed by others

References

Selcuk I, Bozdag G (2013) Recurrence of endometriosis; risk factors, mechanisms and biomarkers; review of the literature. J Turk Ger Gynecol Assoc 14(2):98–103 Buck GM, Hediger ML, Peterson CM et al (2011) Incidence of endometriosis by study population and diagnostic method: the ENDO study. Fertil Steril 96(2):360–365 Bianco B, Andre GM, Vilarino FL et al (2012) The possible role of genetic variants in autoimmune-related genes in the development of endometriosis. Hum Immunol 73(3):306–315 Baldi A, Campioni M, Signorile PG (2008) Endometriosis: pathogenesis, diagnosis, therapy and association with cancer (review). Oncol Rep 19(4):843–846 Sampson J (1927) Peritoneal endometriosis due to dissemination of endometrial tissue into the peritoneal cavity. Am J Obstet Gynecol 14:93–94 Sourial S, Tempest N, Hapangama DK (2014) Theories on the pathogenesis of endometriosis. Int J Reprod Med 11(3):53–65 Wang JR (2008) Beclin1 bridges autophagy, apoptosis and differentiation. Autophagy 4(7):947–948 Eskelinen EL, Saftig P (2009) Autophagy: a lysosomal degradation pathway with a central role in health and disease. Biochim Biophys Acta 1793(4):664–673 Brech A, Ahlquist T, Lothe RA et al (2009) Autophagy in tumour suppression and promotion. Mol Oncol 3(4):366–375 Shen J, Zheng H, Ruan J et al (2013) Autophagy inhibition induces enhanced proapoptotic effects of ZD6474 in glioblastoma. Br J Cancer 109(1):164–171 Klionsky DJ, Abeliovich H, Agostinis P et al (2008) Guidelines for the use and interpretation of assays for monitoring autophagy in higher eukaryotes. Autophagy 4(2):151–175 Heaton NS, Randall G (2011) Dengue virus and autophagy. Viruses 3(8):1332 Yoshimori T, Noda T (2008) Toward unraveling membrane biogenesis in mammalian autophagy. Curr Opin Cell Biol 20(4):401–407 Ghayad SE, Cohen PA (2010) Inhibitors of the PI3K/Akt/mTOR pathway: new hope for breast cancer patients. Recent Pat Anticancer Drug Discov 5(1):29–57 Rakhila H, Al-Akoum M, Doillon C et al (2016) Augmented angiogenic factors expression via FP signaling pathways in peritoneal endometriosis. J Clin Endocr Metab 101(12):4752–4763 Xu H, Zhang T, Man GC et al (2013) Vascular endothelial growth factor C is increased in endometrium and promotes endothelial functions, vascular permeability and angiogenesis and growth of endometriosis. Angiogenesis 16(3):541–551 Lin K, Ma J, Wu R et al (2014) Influence of ovarian endometrioma on expression of steroid receptor RNA activator, estrogen receptors, vascular endothelial growth factor, and thrombospondin 1 in the surrounding ovarian tissues. Reprod Sci 21(2):183–189 Takehara M, Ueda M, Yamashita Y et al (2004) Vascular endothelial growth factor A and C gene expression in endometriosis. Hum Pathol 35(11):1369–1375 Leconte M, Nicco C, Ngô C et al (2011) The mTOR/AKT inhibitor temsirolimus prevents deep infiltrating endometriosis in mice. Am J Pathol 179(2):880–889 Makker A, Goel MM, Das V et al (2012) PI3K-Akt-mTOR and MAPK signaling pathways in polycystic ovarian syndrome, uterine leiomyomas and endometriosis: an update. Gynecol Endocrinol 28(3):175–181 Zhang L, Liu Y, Xu Y et al (2015) The expression of the autophagy gene beclin-1 mRNA and protein in ectopic and eutopic endometrium of patients with endometriosis. Int J Fertil Steril 8(4):429–436 Ren YF, Mu L, Ding XY et al (2010) Decreased expression of Beclin1 in eutopic endometrium of women with adenomyosis. Arch Gyn Obst 282(4):401–406 Hamacher-Brady A, Brady NR, Gottlieb RA (2006) Enhancing macroautophagy protects against ischemia/reperfusion injury in cardiac myocytes. J Biol Chem 281(40):29776–29787 Li YH, Zhang CL (2014) Expression and significance of microtubule associated protein light chain 3 and beclin1 in endometriosis. Chin J Clin Anat 37(2):142–145 Fu LL, Cheng Y, Liu B (2013) Beclin-1: autophagic regulator and therapeutic target in cancer. Int J Biochem Cell Biol 45(5):921–924 Niu TK, Cheng Y, Ren X et al (2010) Interaction of Beclin1 with survivin regulates sensitivity of human glioma cells to TRAIL-induced apoptosis. FEBS Lett 584(16):3519–3524 Katagiri H, Nakayama K, Razia S et al (2015) Loss of autophagy-related protein Beclin1 may define poor prognosis in ovarian clear cell carcinomas. Int J Oncol 47(6):2037–2044 Deng LF, Lei YL, Liu R et al (2013) Pyrvinium targets autophagy addiction to promote cancer cell death. Cell Death Dis 4(5):e614 Liang XH, Jackson S, Seaman M et al (1999) Induction of autophagy and inhibition of tumorigenesis by beclin1. Nature 402(6762):672–676 Du JH, Teng RJ, Guan TJ et al (2012) Role of autophagy in angiogenesis in aortic endothelial cells. Am J Physiol Cell Physiol 302(2):C383 Ramakrishnan S, Nguyen TM, Subramanian IV et al (2007) Autophagy and angiogenesis inhibition. Autophagy 3(3):512–515 Sun Y, Liu JH, Jin L et al (2014) The influence of autophagy-related gene Beclin1 on proliferation, invasion and metastasis of the SKOV3/DDP cells. Progress Obstet Gynecol 23(4):266–269 Tee MK, Vigne JL, Taylor RN (2006) All-trans retinoic acid inhibits vascular endothelial growth factor expression in a cell model of neutrophil activation. Endocrinology 147(3):1264–1270 Suzuki Y, Komi Y, Ashino H et al (2004) Retinoic acid controls blood vessel formation by modulating endothelial and mural cell interaction via suppression of Tie2 signaling in vascular progenitor cells. Blood 104(1):166–169 Li Na, Yanjuan Lu, Li Daoming et al (2017) All-trans retinoic acid suppresses the angiopoietin-Tie2 pathway and inhibits angiogenesis and metastasis in esophageal squamous cell carcinoma. PLoS One 12(4):e0174555 Song ZX, Wang Y, Chen Y (2014) Study of retinoic acid works on mice endometriosis. Prog Obstet Gynecol 23(6):480–482 Peng H, Yuan HQ, Pei J et al (2010) Beneficial effect of all-trans retinoic acid (ATRA) on glomerulosclerosis rats via the down-regulation of the expression of α-smooth muscle actin: a comparative study between ATRA and benazepril. Exp Mol Pathol 89(1):51–57 Huang J, Wei H, Chen G et al (2011) The effect of all-trans retinoic acid (ATRA) on the expression of vascular endothelial growth factor (VEGF) and VEGF receptors of human colon cancer LoVo cell line. Afr J Biotechnol 10(57):12326–12332 Cheng YH, Imir A, Suzuki T et al (2001) SP1 and SP3 mediate progesterone- dependent induction of the 17beta hydroxysteroid dehydrogenase type 2 gene in human endometrium. Biol Reprod 75(4):605–614 Author information Authors and Affiliations Contributions HL: Project development, data collection, manuscript writing. SL: Data collection, animal model. QW: Manuscript writing. Corresponding author Ethics declarations Conflict of interest The authors declare no conflict of interest. Ethical approval This article does not contain any studies with human participants or animals performed by any of the authors. Rights and permissions About this article Cite this article Lu, H., Li, S. & Wu, Q. Retinoic acid regulates endometriotic stromal cell growth through upregulation of Beclin1. Arch Gynecol Obstet 297, 93–99 (2018). https://doi.org/10.1007/s00404-017-4549-8 Received: Accepted: Published: Issue date: DOI: https://doi.org/10.1007/s00404-017-4549-8

Text is read by the "Ask this paper" AI Q&A widget below. Extraction quality varies by source — PMC NXML preserves structure cleanly, OA-HTML may include some navigation residue, and OA-PDF can have broken hyphenation. The publisher copy (via DOI) is the canonical version.

My notes (saved in your browser only)

Ask this paper AI returns verbatim quotes from the full text · source: oa-doi-fallback

Answers must be backed by verbatim quotes from this paper's full text. Hallucinated quotes are dropped automatically; if no verbatim passage answers the question, we say so. How this works

Condition tags

endometriosis

MeSH descriptors

Antineoplastic Agents Cell Proliferation Endometrial Stromal Tumors Endometriosis Stromal Cells Tretinoin Antineoplastic Agents Antineoplastic Agents Autophagy Beclin-1 Beclin-1 Cell Proliferation Endometrial Stromal Tumors Endometrial Stromal Tumors Endometriosis Endometriosis Female Humans Stromal Cells Tretinoin

Citation neighborhood

Papers in the corpus that this work cites (lower rings, blue) and that cite this one (upper rings, green). Dot size scales with the paper's in-corpus citation count — bigger dot = more influential within the endo/adeno field. Click a dot to open that paper. [ expand to 2 hops ] — adds papers reached through this work's immediate citers/citees. Heavier; up to 60 extra dots.

References (37)

Cited by (9)

Source provenance

europepmc
last seen: 2026-07-26T06:08:39.051465+00:00
openalex
last seen: 2026-06-10T17:14:06.276822+00:00
pubmed
last seen: 2026-05-13T22:20:13.663096+00:00
License: CC0 · commercial use OK