scholarly journals TL1A/TNFR2 Axis Enhances Immunoregulatory Effects of Bone Marrow Derived Mesenchymal Stem Cell by Indian Hedgehog Signaling Pathway

2020 ◽  
Author(s):  
Mahmoud Al-Azab ◽  
Williams Walana ◽  
Jing Wei ◽  
Weiping Li ◽  
Yawei Tang ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Signaling Pathway ◽  
Hedgehog Signaling ◽  
Indian Hedgehog ◽  
Hedgehog Signaling Pathway

scholarly journals Downregulation of AAA-domain-containing protein 2 restrains cancer stem cell properties in esophageal squamous cell carcinoma via blockade of the Hedgehog signaling pathway

2020 ◽  
Vol 319 (1) ◽  
pp. C93-C104
Author(s):  
Nuo Li ◽  
Yang Yu ◽  
Baoming Wang
Keyword(s):  
Squamous Cell Carcinoma ◽  
Stem Cell ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cancer Stem Cell ◽  
Cell Carcinoma ◽  
Signaling Pathway ◽  
Squamous Cell ◽  
Colony Formation ◽  
Hedgehog Signaling ◽  
Hedgehog Signaling Pathway

Esophageal squamous cell carcinoma (ESCC) ranks among the five most common cancers in China and has a five-year survival rate of less than 15%. The transcription factor ATPase-family AAA-domain-containing protein 2 (ATAD2) has potential as a therapeutic target in various tumors, and microarray-based gene expression profiling reveals dysregulation of ATAD2 specifically in ESCC. Here we investigated whether ATAD2 could mediate a regulation of cancer stem cell (CSC) biological functions in ESCC. Immunohistochemical staining, reverse transcription quantitative polymerase chain reaction, and Western blot assays all revealed upregulation of ATAD2 in ESCC tissues and cell lines, which furthermore correlated with progression of ESCC. In loss-of-function experiments, silencing of ATAD2 inhibited activation of the Hedgehog signaling pathway, as indicated by reduced expression of glioma-associated oncogene family zinc finger 1 (Gli1), smoothened frizzled class receptor (SMO), and patched 1 (PTCH1). Investigations with 5-ethynyl-2′-deoxyuridine (EdU), Transwell assay, scratch test, flow cytometry, and colony formation assay showed that silencing of ATAD2 or inhibiting the Hedgehog signaling decreased the proliferation, invasion, and migration abilities along with colony formation, but elevated the apoptosis rate of CSCs. Furthermore, in vivo experiments validated the suppressive effect of siRNA-mediated ATAD2 silencing on tumor growth in nude mice. Thus, downregulation of ATAD2 can seemingly restrain the malignant phenotypes of ESCC cells through inhibition of the Hedgehog signaling pathway.

scholarly journals Blockade of TRPM7 Alleviates Chondrocyte Apoptosis and Articular Cartilage Damage in the Adjuvant Arthritis Rat Model Through Regulation of the Indian Hedgehog Signaling Pathway

2021 ◽  
Vol 12 ◽  
Author(s):  
Ganggang Ma ◽  
Yang Yang ◽  
Yong Chen ◽  
Xin Wei ◽  
Jie Ding ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Signaling Pathway ◽  
Rat Model ◽  
Adjuvant Arthritis ◽  
Hedgehog Signaling ◽  
Cartilage Damage ◽  
Chondrocyte Apoptosis ◽  
Indian Hedgehog ◽  
Hedgehog Signaling Pathway ◽  
Articular Cartilage Damage

Articular cartilage damage with subsequent impairment of joint function is a common feature of articular diseases, in particular, rheumatoid arthritis and osteoarthritis. While articular cartilage injury mediated by chondrocyte apoptosis is a known major pathological feature of arthritis, the specific mechanisms remain unclear at present. Transient receptor potential melastatin-like seven channel (TRPM7) is reported to play an important regulatory role in apoptosis. This study focused on the effects of TRPM7 on arthritic chondrocyte injury and its underlying mechanisms of action. Sodium nitroprusside (SNP)-induced rat primary chondrocyte apoptosis and rat adjuvant arthritis (AA) were used as in vitro and in vivo models, respectively. Blockage of TRPM7 with 2-APB or specific siRNA resulted in increased chondrocyte viability and reduced toxicity of SNP. Moreover, treatment with 2-APB enhanced the Bcl-2/Bax ratio and reduced cleaved PARP and IL-6, MMP-13 and ADAMTS-5 expression in SNP-treated chondrocytes. Activation of Indian Hedgehog with purmorphamine reversed the protective effects of 2-APB on SNP-induced chondrocyte apoptosis. Blockage of TRPM7 with 2-APB relieved the clinical signs of AA in the rat model and reduced the arthritis score and paw swelling. Similar to findings in SNP-treated chondrocytes, 2-APB treatment increased the Bcl-2/Bax ratio and suppressed cleaved PARP, IL-6, MMP-13, ADAMTS-5, TRPM7, and Indian hedgehog expression in articular cartilage of AA rats. Our collective findings suggest that blockade of TRPM7 could effectively reduce chondrocyte apoptosis and articular cartilage damage in rats with adjuvant arthritis through regulation of the Indian Hedgehog signaling pathway.

scholarly journals Indian Hedgehog regulates senescence in bone marrow-derived mesenchymal stem cell through modulation of ROS/mTOR/4EBP1, p70S6K1/2 pathway

Aging ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 5693-5715 ◽  
Author(s):  
Mahmoud Al-Azab ◽  
Bing Wang ◽  
Abdalkhalig Elkhider ◽  
Williams Walana ◽  
Weiping Li ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Indian Hedgehog
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