Mesenchymal Stem Cell Conditioned Medium Promotes Proliferation and Migration of Alveolar Epithelial Cells under Septic Conditions In Vitro via the JNK-P38 Signaling Pathway

Abstract

Background/Aims: Mesenchymal stem cell (MSC) based therapies may be useful for treating acute respiratory distress syndrome (ARDS), but the underlying mechanisms are incompletely understood. We investigated the impact of human umbilical cord Wharton's jelly-derived MSC (hUC-MSC) secreted factors on alveolar epithelial cells under septic conditions and determined the relevant intracellular signaling pathways. Methods: Human alveolar epithelial cells (AEC) and primary human small airway epithelial cells (SAEC) were subjected to lipopolysaccharide (LPS) with or without the presence of hUC-MSC-conditioned medium (CM). Proliferation and migration of AEC and SAEC were determined via an MTT assay, a wound healing assay and a transwell migration assay (only for AEC). Protein phosphorylation was determined by western blot and the experiments were repeated in presence of small-molecule inhibitors. The hMSC-secretory proteins were identified by LC-MS/MS mass spectrometry. Results: MSC-CM enhanced proliferation and migration. Activation of JNK and P38, but not ERK, was required for the proliferation and migration of AEC and SAEC. Pretreatment of AEC or SAEC with SP600125, an inhibitor of JNK1 or SB200358, an inhibitor of P38, significantly reduced cell proliferation and migration. An array of proteins including TGF-beta receptor type-1, TGF-beta receptor type-2, Ras-related C3 botulinum toxin substrate 1 and Ras-related C3 botulinum toxin substrate 2 which influencing the proliferation and migration of AEC and SAEC were detected in MSC-CM. Conclusion: Our data suggest MSC promote epithelial cell repair through releasing a repertoire of paracrine factors via activation of JNK and P38 MAPK.

Preconditioning of adipose tissue-derived mesenchymal stem cells with deferoxamine increases the production of pro-angiogenic, neuroprotective and anti-inflammatory factors: Potential application in the treatment of diabetic neuropathy

“…The dose for the secretomes was based on previous reports [38]. Four hours later, glucose level in culture media was raised from basal level (25mM glucose) to hyperglycemic level (45mM glucose).…”

Combined treatment with vitamin C and methotrexate inhibits triple-negative breast cancer cell growth by increasing H2O2 accumulation and activating caspase-3 and p38 pathways

“…p38 phosphorylation in MTX-treated and MTX plus vitamin C-treated cells. The MAPK family kinases ERK, JNK and p38 are involved in cell death, cell differentiation, and cell proliferation (46)(47)(48). In the present study, expression levels of EKR, JNK, p38 and their phosphorylated (activated) forms (p-ERK, p-JNK and p-p38) were estimated by western blotting.…”

Human umbilical cord‐derived mesenchymal stem cells conditioned medium attenuate interstitial fibrosis and stimulate the repair of tubular epithelial cells in an irreversible model of unilateral ureteral obstruction

“…9 Previous studies have shown that MSC-CM promotes proliferation and migration of alveolar epithelial cells under septic conditions. 10 However, few studies have been specially designed to study the effects of MSC secretion factors in kidney diseases.…”

“…More importantly, if the factors secreted by the MSC can slow the progression of CKD, this can overcome the drawbacks of allogeneic MSC transplantation, such as inconvenience, immunological rejection, and MSC tumorigenesis . Previous studies have shown that MSC‐CM promotes proliferation and migration of alveolar epithelial cells under septic conditions . However, few studies have been specially designed to study the effects of MSC secretion factors in kidney diseases.…”