PMID- 37307020
OWN - NLM
STAT- MEDLINE
DCOM- 20230921
LR  - 20230929
IS  - 1557-7732 (Electronic)
IS  - 1080-7683 (Linking)
VI  - 39
IP  - 7
DP  - 2023 Sep
TI  - Activation of Sonic Hedgehog Signaling Pathway Regulates Human Trabecular 
      Meshwork Cell Function.
PG  - 430-438
LID - 10.1089/jop.2023.0022 [doi]
AB  - Purpose: To investigate the effects of Sonic hedgehog (Shh) signaling on primary 
      human trabecular meshwork (HTM) cells. Methods: Primary HTM cells were isolated 
      from healthy donors and cultured. Recombinant Shh (rShh) protein and cyclopamine 
      were used to activate and inhibit the Shh signaling pathway, respectively. A cell 
      viability assay was performed to assess the effects of rShh on the activity of 
      primary HTM cells. Functional assessment of cell adhesion and phagocytosis was 
      also performed. The proportion of apoptotic cells was examined using flow 
      cytometry. Fibronectin (FN) and transforming growth factor beta2 (TGF-beta2) protein 
      were detected to assess the influence of rShh on the metabolism of the 
      extracellular matrix (ECM). Real-time polymerase chain reaction (RT-PCR) and 
      western blot analyses were used to examine mRNA and protein expression of Shh 
      signaling pathway-associated factors GLI Family Zinc Finger 1 (GLI1) and 
      Suppressor of Fused (SUFU). Results: rShh significantly enhanced primary HTM cell 
      viability at a concentration of 0.5 mug/mL. rShh increased the adhesion and 
      phagocytic abilities of primary HTM cells, and decreased cell apoptosis. FN and 
      TGF-beta2 protein expression increased in primary HTM cells treated with rShh. rShh 
      upregulated the transcriptional activity and protein levels of GLI1, and 
      downregulated those of SUFU. Correspondingly, the rShh-induced GLI1 upexpression 
      was partially blocked by pretreatment with the Shh pathway inhibitor cyclopamine 
      at a concentration of 10 muM. Conclusions: Activation of Shh signaling can 
      regulate the function of primary HTM cells through GLI1. Regulation of Shh 
      signaling may be a potential target for attenuating cell damage in glaucoma.
FAU - Wang, Xiaochen
AU  - Wang X
AUID- ORCID: 0000-0003-2348-5955
AD  - Department of Ophthalmology, The First Affiliated Hospital of Chongqing Medical 
      University, Chongqing, China.
AD  - Chongqing Key Lab of Ophthalmology, Chongqing Eye Institute, Chongqing Branch of 
      National Clinical Research Center for Ocular Diseases, Chongqing, China.
FAU - Tan, Sisi
AU  - Tan S
AUID- ORCID: 0000-0001-8387-4149
AD  - Department of Ophthalmology, The First Affiliated Hospital of Chongqing Medical 
      University, Chongqing, China.
AD  - Chongqing Key Lab of Ophthalmology, Chongqing Eye Institute, Chongqing Branch of 
      National Clinical Research Center for Ocular Diseases, Chongqing, China.
FAU - Yang, Shuang
AU  - Yang S
AUID- ORCID: 0000-0002-7943-8130
AD  - Department of Ophthalmology, The First Affiliated Hospital of Chongqing Medical 
      University, Chongqing, China.
AD  - Chongqing Key Lab of Ophthalmology, Chongqing Eye Institute, Chongqing Branch of 
      National Clinical Research Center for Ocular Diseases, Chongqing, China.
FAU - Liu, Xianmao
AU  - Liu X
AUID- ORCID: 0000-0002-6510-9109
AD  - Department of Ophthalmology, The First Affiliated Hospital of Chongqing Medical 
      University, Chongqing, China.
AD  - Chongqing Key Lab of Ophthalmology, Chongqing Eye Institute, Chongqing Branch of 
      National Clinical Research Center for Ocular Diseases, Chongqing, China.
FAU - Lei, Junqin
AU  - Lei J
AUID- ORCID: 0000-0001-5938-5812
AD  - Department of Ophthalmology, The First Affiliated Hospital of Chongqing Medical 
      University, Chongqing, China.
AD  - Chongqing Key Lab of Ophthalmology, Chongqing Eye Institute, Chongqing Branch of 
      National Clinical Research Center for Ocular Diseases, Chongqing, China.
FAU - Li, Hong
AU  - Li H
AUID- ORCID: 0000-0002-8240-7060
AD  - Department of Ophthalmology, The First Affiliated Hospital of Chongqing Medical 
      University, Chongqing, China.
AD  - Chongqing Key Lab of Ophthalmology, Chongqing Eye Institute, Chongqing Branch of 
      National Clinical Research Center for Ocular Diseases, Chongqing, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230612
PL  - United States
TA  - J Ocul Pharmacol Ther
JT  - Journal of ocular pharmacology and therapeutics : the official journal of the 
      Association for Ocular Pharmacology and Therapeutics
JID - 9511091
RN  - 0 (Hedgehog Proteins)
RN  - 0 (Transforming Growth Factor beta2)
RN  - 0 (Zinc Finger Protein GLI1)
RN  - 0 (SHH protein, human)
SB  - IM
MH  - Humans
MH  - *Hedgehog Proteins/genetics/metabolism
MH  - Signal Transduction
MH  - Trabecular Meshwork/metabolism
MH  - *Transforming Growth Factor beta2/metabolism
MH  - Zinc Finger Protein GLI1/genetics/metabolism/pharmacology
OTO - NOTNLM
OT  - IOP
OT  - Shh
OT  - glaucoma
OT  - trabecular meshwork cells
EDAT- 2023/06/12 13:07
MHDA- 2023/09/20 06:42
CRDT- 2023/06/12 11:43
PHST- 2023/09/20 06:42 [medline]
PHST- 2023/06/12 13:07 [pubmed]
PHST- 2023/06/12 11:43 [entrez]
AID - 10.1089/jop.2023.0022 [doi]
PST - ppublish
SO  - J Ocul Pharmacol Ther. 2023 Sep;39(7):430-438. doi: 10.1089/jop.2023.0022. Epub 
      2023 Jun 12.