Biology subjects

Jung, J. Y.

Publications and source records attributed to Jung, J. Y..

4 recordsLinked to original sources

bioRxiv2021

Nodal is a short-range morphogen with activity that spreads through a relay mechanism in human gastruloids

Morphogens are signaling molecules that convey positional information and dictate cell fates during development. Little is known about how morphogen gradients are created and interpreted during mammalian embryogenesis. Here we take advantage of a human gastruloid model to visualize endogenous Nodal protein in living cells. We show that Nodal is extremely short range so that Nodal protein is limited to the immediate neighborhood of source cells. Nodal activity spreads through a relay mechanism in which Nodal production induces neighboring cells to transcribe Nodal. We further show that the Nodal inhibitor Lefty, while biochemically capable of long-range diffusion, also acts locally to control the timing of Nodal spread and therefore of mesoderm differentiation during patterning. Our study establishes a novel paradigm for tissue patterning by an activator-inhibitor pair.

developmental biology↗

bioRxiv2020

Human relevance of blocking the Rac1-TRPC5 pathway as a podocyte-protective strategy for progressive kidney diseases

Podocyte injury and the appearance of proteinuria are key features of several progressive kidney diseases. Genetic deletion or selective inhibition of TRPC5 channels with small-molecule inhibitors protects podocytes in rodent models of disease, but less is known about the human relevance and translatability of TRPC5 inhibition. Here, we investigate the effect of TRPC5 inhibition in puromycin aminonucleoside (PAN)-treated human iPSC-derived podocytes and kidney organoids. We first established that systemic administration of the TRPC5-specific blocker AC1903 was sufficient to protect podocyte cytoskeletal proteins and suppress proteinuria in PAN-induced nephrosis in rats, an established model of podocyte injury and progressive kidney disease. PAN treatment also triggered the Rac1-TRPC5 injury pathway in human iPSC-derived podocytes and kidney organoids. TRPC5 current was recorded in human iPSC-derived podocytes, and was blocked by AC1903. The TRPC5 blocker also reversed the effects of PAN-induced injury in human podocytes in both 2D and 3D culture systems. Taken together, these results revealed the relevance of the TRPC5-Rac1 pathway in human kidney tissue highlighting the potential of this therapeutic strategy for patients.

cell biology↗

bioRxiv2020

Targeted Eicosanoid Profiling Reveals MicroRNA-155 Shifts PGE2/PGD2 Balance Towards Oncogenic State

microRNA-155 is a strong oncogenic microRNAs with multiple functions. To reveal its novel function in cancer metabolism, we performed a targeted metabolomic analysis of icosanoids, the key metabolites of inflammation-related carcinogenesis. We found miR-155-depleted cells expressed unbalanced prostaglandins, especially in PGE2 and PGD2. Subsequent analysis of primary cancer cells and 20 TNBC specimen indicated a positive correlation between miR-155 and PGE2/PGD2 ratio. Mechanistically, miR-155 controls the prostaglandin shift by up-regulating PGE2-producing enzymes PTGES/PTGES2 and down-regulating PGD2-producing enzyme PTGDS. Further analysis showed that the up-regulation of PTGES2 is driven by miR-155-cMYC axis whereas PTGES is transactivated by miR-155-KLF4 axis, indicating a dual-regulatory mode for the metabolic enzyme expression drives a shift in PGE2/PGD2 balance. Lastly, we show the miR-155-driven cellular proliferation is significantly restored by the siRNA of PTGES1/2, of which expression also correlates with patients survival. Taken altogether, our study reveals an unprecedented oncogenic function of miR-155 on prostaglandin regulation.

cancer biology↗

bioRxiv2019

Assortment of Stauntonia hexaphylla and Cornus officinalis protect against testosterone-induced benign prostatic hyperplasia through anti-inflammatory and anti-proliferative activity

Benign prostatic hyperplasia (BPH) is a progressive pathological condition associated with proliferation of prostatic tissues, prostate enlargement, and lower-urinary tract symptoms. However, the mechanism underlying the pathogenesis of BPH is not clear. The aim of this study was to investigate the protective effects of Stauntonia hexaphylla and Cornus officinalis (SC extract) on a testosterone propionate (TP)-induced BPH model. For in vitro experiments, a human prostate adenocarcinoma cell line was used to perform western blotting for androgen receptor (AR), prostate specific antigen (PSA), and 5-reductase type 2. Male Sprague-Dawley rats were randomly divided into 8 groups as follows for the in vivo experiments: control, BPH, Fina, Saw, SC25, SC50, SC100, and SC200. To induce BPH, all rats, except those in the control group, were daily administered with subcutaneous injections of TP (5 mg/kg), and orally treated with appropriate PBS/drugs for 4 consecutive weeks. Our findings indicated that the SC treatment significantly reduced the prostate size and downregulated the serum testosterone and DHT levels in BPH rats. The histological examination revealed that SC treatment markedly recovered the TP-induced abnormalities and reduced the prostatic hyperplasia. In addition, in vitro and in vivo western blotting indicated that SC treatment significantly downregulated the AR, PSA, and 5-reductase type 2 expression, while an immunohistochemistry examination revealed that the SC extract significantly reduced the expression of type 2 5-reductase and proliferating cell nuclear antigen positive cell count. Collectively, our findings demonstrated that SC extract attenuates BPH through anti-proliferative and anti-inflammation activities and might be useful in the clinical treatment of BPH.

cancer biology↗